1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/18400190.csml convertedTime:2009.07.01.11:18

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Cytokine signaling modules in inflammatory responses.
Authors O'Shea JJ, Murray PJ.
Affiliation Molecular Immunology and Inflammation Branch, National Institute of Arthritis,Musculoskeletal and Skin Diseases, National Institutes of Health, Bethesda, MD20852, USA. osheajo@mail.nih.gov
Abstract Cytokine signaling via a restricted number of Jak-Stat pathways positively andnegatively regulates all cell types involved in the initiation, propagation, andresolution of inflammation. Here, we focus on Jak-Stat signaling in three majorcell types involved in inflammatory responses: T cells, neutrophils, andmacrophages. We summarize how the Jak-Stat pathways in these cells arenegatively regulated by the Suppressor of cytokine signaling (Socs) proteins. Weemphasize that common Jak-Stat-Socs signaling modules can have diversedevelopmental, pro- and anti-inflammatory outcomes depending on the cytokinereceptor activated and which genes are accessible at a given time in a cell'slife. Because multiple components of Jak-Stat-Socs pathways are mutated orclosely associated with human inflammatory diseases, and cytokine-basedtherapies are increasingly deployed to treat inflammation, understandingcytokine signaling will continue to advance our ability to manipulate chronicand acute inflammatory diseases.
PMID 18400190
Model Abstract

Entity

G010228:IFN-beta G010539:SOCS1 G011174:IL21 G011175:IL22 G011341:IL17 G011345:IL10 G011523:RORA G011587:FOXP3 G011948:SOCS3 G016992:IFN-alpha MO000000011:ERK MO000000022:p38 MO000000147:Jak3 MO000001935:Btk MO000003473:G-CSF MO000007327:IL-17 MO000013119:STAT1 MO000013122:STAT3 MO000013126:STAT5A MO000013130:STAT6 MO000013133:STAT5B MO000016656:STATs MO000016658:IFN Type I MO000016659:IFNalpha MO000016660:IFNbeta MO000016830:IL-7 MO000016855:FAK family MO000016876:STAT5 MO000016894:MAPK MO000017004:SOCS-1 MO000017053:IL-4 MO000017061:IL-2 MO000017121:SOCS-3 MO000017157:CXCR4 MO000017181:STAT4 MO000017247:IL-10 MO000017265:IL-12 MO000017443:TGFbeta1 MO000018946:elongin C MO000018947:elongin B MO000019001:CXCL12 MO000019387:cytokines MO000019479:protein remnants MO000019517:IL-22 MO000062893:IL27 MO000068831:MAL MO000089770:GCSFR e1: e10: e11:cytokine: cytokine receptor: Jak1: Jak2 e12:cytokine: cytokine receptor {pY}: Jak1: Jak2 e13:cytokine: cytokine receptor {pY}: Jak1: Jak2: STATs e14:STATs {nuclear} e15:STATs {nuclear}: DNA e16:DNA e17:IL-7R: gamma-c e18:IL-7: IL-7R: gamma-c e19:IL-6: IL-6R: gp130 e2: e20:STAT5{activated} e21:STAT5A {activated} e22:STAT5B {activated} e23:STAT4 {activated} e24:STAT6 {activated} e25:STAT5{nuclear}} e26:FOXP3 gene e27:STAT5{nuclear}: FOXP3 gene e28:STAT3 {activated} e29:IL23: IL23R: gp130 e3: e30:IL-21: IL-21R:gamma-c e31:STAT3 {nuclear} e32:IL21 gene e33:IL17gene e34:STAT3 {nuclear}: IL21gene e35:STAT3 {nuclear}: IL17gene e36:RORC e37:SOCS e38:culin e39:Rbx2 e4: e40:E3 ubiquitin ligase e41:SOCS e42:cytokine: cytokine receptor {pY}: Jak1: Jak2: STATs: E3 ubiquitin ligase e43:cytokine: cytokine receptor {pY} {ub}: Jak1: Jak2: STATs: E3 ubiquitin ligase e44:G-CSF: GCSFR e45:MAPK {activated} e46:G-CSF: GCSFR: SOCS-3 e47:AIR e48:IL-6: IL-6R: gp130: STAT3 e49:IL-6: IL-6R: gp130: STAT3 e5:cytokine receptor: Jak1: Jak2 e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:cytokine: cytokine receptor: Jak1: Jak2 e60: e61: e62: e63:IL23: IL23R: gp130: STAT3 e64:IL23: IL23R: gp130: STAT3{activated} e65:IL-6: IL-6R: gp130: SOCS3 e66:IL23: IL23R: gp130: SOCS3 e67:IL-10: IL-10R e68:S1008A e69:TLR ligand: TLR e7: e70:MAL {p} e71:MAL{p}: SOSC-1 e72:CXCR4 {activated} e73:FAK {p} e74:p38 {activated} e75:zymosan e76:ERK {activated} e77:STAT1 {activated} e8: e9:

Process

p1 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p2 p20 p21 p22 p23 p24 p25 p26 p27 p28 p29 p3 p30 p31 p32 p33 p34 p35 p36 p37 p38 p39 p4 p40 p41 p42 p43 p44 p45 p46 p47 p48 p49 p5 p50 p51 p52 p53 p54 p55 p56 p57 p58 p59 p6 p60 p61 p62 p63 p64 p65 p66 p67 p68 p69 p7 p70 p71 p72 p73 p74 p8 p9
Model Detail
885.0, 1001.0
30.0, 30.0

IFN-beta

--

G010228

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p60

true true true true

csml-variable:Double

m93217

10

false

infinite

0

unit false false false
TRANSFACG010228

--

Go back
746.0, 862.0
28.0, 28.0

SOCS1

--

G010539

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p58

--

true true true true

csml-variable:Double

m93501

10

false

infinite

0

unit false false false
TRANSFACG010539

--

Go back
869.0, 1095.0
30.0, 30.0

IL21

--

G011174

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p28

--

true true true true

csml-variable:Double

m94059

10

false

infinite

0

unit false false false
TRANSFACG011174

--

Go back
550.0, 1002.0
28.0, 28.0

IL22

--

G011175

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p35

--

true true true true

csml-variable:Double

m94060

10

false

infinite

0

unit false false false
TRANSFACG011175

--

Go back
586.0, 1178.0
28.0, 28.0

IL17

--

G011341

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p29

p21

true true true true

csml-variable:Double

m94226

10

false

infinite

0

unit false false false
TRANSFACG011341

--

Go back
810.0, 958.0
28.0, 28.0

IL10

--

G011345

cso30:c:mRNA

cso30:i:CC_CellComponent

--

--

p68 p69 p72

true true true true

csml-variable:Double

m94230

10

false

infinite

0

unit false false false
TRANSFACG011345

--

Go back
783.0, 1061.0
26.5, 26.5

RORA

--

G011523

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p31

p32

true true true true

csml-variable:Double

m94396

10

false

infinite

0

unit false false false
TRANSFACG011523

--

Go back
750.0, 970.0
28.0, 28.0

FOXP3

--

G011587

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p12

--

true true true true

csml-variable:Double

m94442

10

false

infinite

0

unit false false false
TRANSFACG011587

--

Go back
824.0, 1132.0
30.0, 30.0

SOCS3

--

G011948

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p48

--

true true true true

csml-variable:Double

m94757

10

false

infinite

0

unit false false false
TRANSFACG011948

--

Go back
882.0, 962.0
28.0, 28.0

IFN-alpha

--

G016992

cso30:c:mRNA

cso30:i:CC_CellComponent

--

--

p59

true true true true

csml-variable:Double

m98717

10

false

infinite

0

unit false false false
TRANSPATHG016992

--

Go back
957.0, 697.0
30.0, 30.0

ERK

--

MO000000011

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p70

true true true true

csml-variable:Double

m76

10

false

infinite

0

unit false false false
TRANSPATHMO000000011

--

Go back
967.0, 802.0
26.0, 26.0

p38

--

MO000000022

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p67

true true true true

csml-variable:Double

m74

10

false

infinite

0

unit false false false
TRANSPATHMO000000022

--

Go back
434.0, 618.0
28.0, 28.0

Jak3

--

MO000000147

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p11

true true true true

csml-variable:Double

m131

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000000147

--

Go back
785.0, 608.0
32.0, 32.0

Btk

--

MO000001935

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p62

true true true true

csml-variable:Double

m367

10

false

infinite

0

unit false false false
InterProIPR001452
TRANSPATHMO000001935

--

Go back
730.0, 80.0
28.0, 28.0

G-CSF

--

MO000003473

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p42

true true true true

csml-variable:Double

m464

10

false

infinite

0

unit false false false
InterProIPR003629
TRANSPATHMO000003473

--

Go back
530.0, 1242.0
27.0, 27.0

IL-17

--

MO000007327

cso30:c:Protein

cso30:i:CC_CellComponent

--

p21

--

true true true true

csml-variable:Double

m840

10

false

infinite

0

unit false false false
TRANSPATHMO000007327

--

Go back
896.0, 612.0
32.0, 32.0

STAT1

--

MO000013119

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p71

true true true true

csml-variable:Double

m1357

10

false

infinite

0

unit false false false
InterProIPR008967
TRANSPATHMO000013119

--

Go back
371.0, 1027.0
34.0, 34.0

STAT3

--

MO000013122

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p24 p36 p44 p50 p51 p52 p73

true true true true

csml-variable:Double

m1360

10

false

infinite

0

unit false false false
InterProIPR008967
TRANSPATHMO000013122

--

Go back
354.0, 630.0
28.5, 28.5

STAT5A

--

MO000013126

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p9

true true true true

csml-variable:Double

m1364

10

false

infinite

0

unit false false false
InterProIPR000923
TRANSPATHMO000013126

--

Go back
335.0, 885.0
30.0, 30.0

STAT6

--

MO000013130

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p14

true true true true

csml-variable:Double

m1368

10

false

infinite

0

unit false false false
InterProIPR008967
TRANSPATHMO000013130

--

Go back
354.0, 710.0
28.0, 28.0

STAT5B

--

MO000013133

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p10

true true true true

csml-variable:Double

m1371

10

false

infinite

0

unit false false false
InterProIPR008967
TRANSPATHMO000013133

--

Go back
395.0, 260.0
28.0, 28.0

STATs

--

MO000016656

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p4 p5

true true true true

csml-variable:Double

m1633

10

false

infinite

0

unit false false false
TRANSPATHMO000016656

--

Go back
142.0, 754.0
27.0, 27.0

IFN Type I

--

MO000016658

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p17

true true true true

csml-variable:Double

m1634

10

false

infinite

0

unit false false false
TRANSPATHMO000016658

--

Go back
966.0, 906.0
28.0, 28.0

IFNalpha

--

MO000016659

cso30:c:Protein

cso30:i:CC_CellComponent

--

p59

--

true true true true

csml-variable:Double

m1635

10

false

infinite

0

unit false false false
InterProIPR000471
TRANSPATHMO000016659

--

Go back
965.0, 1081.0
30.0, 30.0

IFNbeta

--

MO000016660

cso30:c:Protein

cso30:i:CC_CellComponent

--

p60

--

true true true true

csml-variable:Double

m1636

10

false

infinite

0

unit false false false
InterProIPR000471
TRANSPATHMO000016660

--

Go back
79.0, 539.0
26.0, 26.0

IL-7

--

MO000016830

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p7

true true true true

csml-variable:Double

m1767

10

false

infinite

0

unit false false false
InterProIPR001181
TRANSPATHMO000016830

--

Go back
954.0, 506.0
27.0, 27.0

FAK family

--

MO000016855

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p65

true true true true

csml-variable:Double

m1787

10

false

infinite

0

unit false false false
TRANSPATHMO000016855

--

Go back
360.0, 536.0
32.0, 32.0

STAT5

--

MO000016876

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p8 p33 p43

true true true true

csml-variable:Double

m1798

10

false

infinite

0

unit false false false
TRANSPATHMO000016876

--

Go back
587.0, 467.0
34.0, 34.0

MAPK

--

MO000016894

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p46

true true true true

csml-variable:Double

m1812

10

false

infinite

0

unit false false false
TRANSPATHMO000016894

--

Go back
432.0, 668.0
32.0, 32.0

SOCS-1

--

MO000017004

cso30:c:Protein

cso30:i:CC_CellComponent

--

p63

p8 p9 p10 p11 p21 p24 p61

true true true true

csml-variable:Double

m1906

10

false

infinite

0

unit false false false
InterProIPR001496
TRANSPATHMO000017004

--

Go back
158.0, 887.0
28.0, 28.0

IL-4

--

MO000017053

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p14 p58

true true true true

csml-variable:Double

m1947

10

false

infinite

0

unit false false false
InterProIPR001325
TRANSPATHMO000017053

--

Go back
135.0, 419.0
26.0, 26.0

IL-2

--

MO000017061

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p33

true true true true

csml-variable:Double

m1954

10

false

infinite

0

unit false false false
TRANSPATHMO000017061

--

Go back
827.0, 231.0
25.0, 25.0

SOCS-3

--

MO000017121

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p45 p55 p56

true true true true

csml-variable:Double

m2005

10

false

infinite

0

unit false false false
InterProIPR001496
TRANSPATHMO000017121

--

Go back
801.0, 457.0
30.0, 30.0

CXCR4

--

MO000017157

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p64

true true true true

csml-variable:Double

m2033

10

false

infinite

0

unit false false false
InterProIPR000276
TRANSPATHMO000017157

--

Go back
334.0, 808.0
28.0, 28.0

STAT4

--

MO000017181

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p13 p17

true true true true

csml-variable:Double

m2053

10

false

infinite

0

unit false false false
InterProIPR008967
TRANSPATHMO000017181

--

Go back
893.0, 781.0
30.0, 30.0

IL-10

--

MO000017247

cso30:c:Protein

cso30:i:CC_CellComponent

--

p68 p69 p72 p74

--

true true true true

csml-variable:Double

m2103

10

false

infinite

0

unit false false false
InterProIPR000098
TRANSPATHMO000017247

--

Go back
160.0, 807.0
29.0, 29.0

IL-12

--

MO000017265

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p13

true true true true

csml-variable:Double

m2121

10

false

infinite

0

unit false false false
TRANSPATHMO000017265

--

Go back
37.0, 977.0
30.0, 30.0

TGFbeta1

--

MO000017443

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p34

true true true true

csml-variable:Double

m2269

10

false

infinite

0

unit false false false
InterProIPR002400
TRANSPATHMO000017443

--

Go back
607.0, 361.0
30.0, 30.0

elongin C

--

MO000018946

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p38

true true true true

csml-variable:Double

m3558

10

false

infinite

0

unit false false false
InterProIPR001232
TRANSPATHMO000018946

--

Go back
602.0, 312.0
31.0, 31.0

elongin B

--

MO000018947

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p38

true true true true

csml-variable:Double

m3559

10

false

infinite

0

unit false false false
InterProIPR000626
TRANSPATHMO000018947

--

Go back
951.0, 459.0
26.0, 26.0

CXCL12

--

MO000019001

cso30:c:Protein

cso30:i:CC_CellComponent

--

p66

p64 p65

true true true true

csml-variable:Double

m3609

10

false

infinite

0

unit false false false
InterProIPR001811
TRANSPATHMO000019001

--

Go back
405.0, 79.0
28.0, 28.0

cytokines

--

MO000019387

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p3

true true true true

csml-variable:Double

m3957

10

false

infinite

0

unit false false false
TRANSPATHMO000019387

--

Go back
437.0, 417.0
30.0, 30.0

protein remnants

--

MO000019479

cso30:c:Protein

cso30:i:CC_CellComponent

--

p41 p63

--

true true true true

csml-variable:Double

m360980

10

false

infinite

0

unit false false false
TRANSPATHMO000019479

--

Go back
313.0, 1437.0
30.0, 30.0

IL-22

--

MO000019517

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p36 p57

true true true true

csml-variable:Double

m4068

10

false

infinite

0

unit false false false
TRANSPATHMO000019517

--

Go back
1090.0, 610.0
35.0, 35.0

IL27

--

MO000062893

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p71 p73

true true true true

csml-variable:Double

m37778

10

false

infinite

0

unit false false false
TRANSPATHMO000062893

--

Go back
654.0, 610.0
28.0, 28.0

MAL

--

MO000068831

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p62

true true true true

csml-variable:Double

m43675

10

false

infinite

0

unit false false false
TRANSPATHMO000068831

--

Go back
603.0, 171.0
34.0, 34.0

GCSFR

--

MO000089770

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p42

true true true true

csml-variable:Double

m63352

10

false

infinite

0

unit false false false
TRANSPATHMO000089770

--

Go back
228.32757526204472, 142.33337188136923
837.8133079645139, 1265.56712085971

--

e1

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane

--

--

--

true true true true

csml-variable:Double

m1

0

false

infinite

0

unit false true false

--

Go back
236.39984814925893, 161.67697930985744
812.0976560385449, 1188.4662849165795

--

e10

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytosol

--

--

--

true true true true

csml-variable:Double

m10

0

false

infinite

0

unit false true false

--

Go back
238.375, 181.5
27.44359789519843, 53.11664108748083

cytokine: cytokine receptor: Jak1: Jak2

--

e11

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p1

p2

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
244.375, 250.5
24.582163999122997, 47.57838193378645

cytokine: cytokine receptor {pY}: Jak1: Jak2

--

e12

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p2

p4

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
240.875, 303.5
32.25, 45.0

cytokine: cytokine receptor {pY}: Jak1: Jak2: STATs

--

e13

cso30:c:Complex

cso30:i:CC_Cytosol

--

p4

p39

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
525.0, 914.0
28.0, 28.0

STATs {nuclear}

--

e14

cso30:c:Protein

cso30:i:CC_CellComponent

--

p5

p6

true true true true

csml-variable:Double

m14

10

false

infinite

0

unit false false false
TRANSPATHMO000016656

--

Go back
569.5, 977.625
45.0, 12.75

STATs {nuclear}: DNA

--

e15

cso30:c:Complex

cso30:i:CC_NuclearChromosome

--

p6

p37

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
489.5, 955.125
45.0, 9.75

DNA

--

e16

cso30:c:Dna

cso30:i:CC_Nucleoplasm

--

--

p6

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
240.5, 481.0
30.848525245792366, 37.7737043826029

IL-7R: gamma-c

--

e17

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p7

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
239.875, 529.5
32.25, 45.0

IL-7: IL-7R: gamma-c

--

e18

cso30:c:Complex

cso30:i:CC_Cytosol

--

p7

p8 p9 p10

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
229.875, 972.5
29.472242613323544, 41.12405946045146

IL-6: IL-6R: gp130

--

e19

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p53

p34 p35 p51 p55

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
228.32757526204472, 142.33337188136923
837.8133079645139, 1265.56712085971

--

e2

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m2

0

false

infinite

0

unit false true false

--

Go back
360.0, 584.0
32.0, 32.0

STAT5{activated}

--

e20

cso30:c:Protein

cso30:i:CC_CellComponent

--

p8 p33 p43

p11 p18 p32

true true true true

csml-variable:Double

m20

10

false

infinite

0

unit false false false
TRANSPATHMO000016876

--

Go back
354.0, 670.0
28.5, 28.5

STAT5A {activated}

--

e21

cso30:c:Protein

cso30:i:CC_CellComponent

--

p9

p20

true true true true

csml-variable:Double

m21

10

false

infinite

0

unit false false false
InterProIPR000923
TRANSPATHMO000013126

--

Go back
354.0, 750.0
28.0, 28.0

STAT5B {activated}

--

e22

cso30:c:Protein

cso30:i:CC_CellComponent

--

p10

p20

true true true true

csml-variable:Double

m22

10

false

infinite

0

unit false false false
InterProIPR008967
TRANSPATHMO000013133

--

Go back
334.0, 848.0
28.0, 28.0

STAT4 {activated}

--

e23

cso30:c:Protein

cso30:i:CC_CellComponent

--

p13 p17

p15

true true true true

csml-variable:Double

m23

10

false

infinite

0

unit false false false
InterProIPR008967
TRANSPATHMO000017181

--

Go back
333.0, 921.0
30.0, 30.0

STAT6 {activated}

--

e24

cso30:c:Protein

cso30:i:CC_CellComponent

--

p14

p16

true true true true

csml-variable:Double

m24

10

false

infinite

0

unit false false false
InterProIPR008967
TRANSPATHMO000013130

--

Go back
556.0, 868.0
32.0, 32.0

STAT5{nuclear}}

--

e25

cso30:c:Protein

cso30:i:CC_CellComponent

--

p18

p19

true true true true

csml-variable:Double

m25

10

false

infinite

0

unit false false false
TRANSPATHMO000016876

--

Go back
709.5, 891.125
45.0, 9.75

FOXP3 gene

--

e26

cso30:c:Dna

cso30:i:CC_Nucleoplasm

--

--

p19

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
672.5, 908.625
45.0, 12.75

STAT5{nuclear}: FOXP3 gene

--

e27

cso30:c:Complex

cso30:i:CC_Nucleoplasm

--

p19

p12

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false false false

--

Go back
439.0, 1203.0
34.0, 34.0

STAT3 {activated}

--

e28

cso30:c:Protein

cso30:i:CC_CellComponent

--

p24 p36 p44 p50 p73

p27 p64 p65

true true true true

csml-variable:Double

m28

10

false

infinite

0

unit false false false
InterProIPR008967
TRANSPATHMO000013122

--

Go back
232.625, 1144.5
31.099608398600232, 38.08115314114314

IL23: IL23R: gp130

--

e29

cso30:c:Complex

cso30:i:CC_Cytosol

--

p54

p52 p56

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
245.08384142133502, 159.76542588770133
804.3007756459339, 1230.7030128470474

--

e3

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m3

0

false

infinite

0

unit false true false

--

Go back
233.625, 1294.5
28.87047992001333, 35.351608065322445

IL-21: IL-21R:gamma-c

--

e30

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p21 p24

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false false false

--

Go back
495.0, 1055.0
34.0, 34.0

STAT3 {nuclear}

--

e31

cso30:c:Protein

cso30:i:CC_CellComponent

--

p27 p53 p54

p25 p26 p30 p31 p48 p49 p74

true true true true

csml-variable:Double

m31

10

false

infinite

0

unit false false false
InterProIPR008967
TRANSPATHMO000013122

--

Go back
621.5, 1077.125
45.0, 9.75

IL21 gene

--

e32

cso30:c:Dna

cso30:i:CC_Nucleoplasm

--

--

p25

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
533.5, 1167.125
45.0, 9.75

IL17gene

--

e33

cso30:c:Dna

cso30:i:CC_Nucleoplasm

--

--

p26

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
733.5, 1103.625
45.0, 12.75

STAT3 {nuclear}: IL21gene

--

e34

cso30:c:Complex

cso30:i:CC_Nucleoplasm

--

p25

p28

true true true true

csml-variable:Double

m34

0

false

infinite

0

unit false false false

--

Go back
609.5, 1145.625
45.0, 12.75

STAT3 {nuclear}: IL17gene

--

e35

cso30:c:Complex

cso30:i:CC_Nucleoplasm

--

p26

p29

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false false false

--

Go back
725.0, 1027.0
30.0, 30.0

RORC

--

e36

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p30

p32

true true true true

csml-variable:Double

m36

10

false

infinite

0

unit false false false
Affymetrix1425792_a_at
EnsemblENSMUSG00000028150
MGDRorc
ProteomeHumanPSD/Rorc
RefSeqNM_011281
TRANSFACG009892
UnigeneMm.4372

--

Go back
693.5, 938.0
36.79930795847751, 19.62629757785467

SOCS

--

e37

cso30:c:mRNA

cso30:i:CC_Cytosol

--

p37

--

true true true true

csml-variable:Double

m37

0

false

infinite

0

unit false false false

--

Go back
466.5, 316.125
39.31273898168646, 24.242855705373312

culin

--

e38

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p38

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
467.5, 358.125
36.2, 27.149999999999995

Rbx2

--

e39

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p38

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false false false

--

Go back
276.08293381602215, 190.2715203987824
742.3025908565597, 1169.6908238248843

--

e4

cso30:c:EntityBiologicalCompartment

cso30:i:CC_PlasmaMembrane_InternalSideOfPlasmaMembrane_

--

--

--

true true true true

csml-variable:Double

m4

0

false

infinite

0

unit false true false

--

Go back
539.875, 385.5
32.25, 45.0

E3 ubiquitin ligase

--

e40

cso30:c:Complex

cso30:i:CC_Cytosol

--

p38

p39

true true true true

csml-variable:Double

m40

0

false

infinite

0

unit false false false

--

Go back
540.125, 244.5
24.34710203260213, 39.48178707989535

SOCS

--

e41

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p38

true true true true

csml-variable:Double

m41

0

false

infinite

0

unit false false false

--

Go back
237.875, 356.5
30.829555881813178, 43.017984951367225

cytokine: cytokine receptor {pY}: Jak1: Jak2: STATs: E3 ubiquitin ligase

--

e42

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p39

p40

true true true true

csml-variable:Double

m42

0

false

infinite

0

unit false false false

--

Go back
236.875, 407.5
32.25, 45.0

cytokine: cytokine receptor {pY} {ub}: Jak1: Jak2: STATs: E3 ubiquitin ligase

--

e43

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p40

p41

true true true true

csml-variable:Double

m43

0

false

infinite

0

unit false false false

--

Go back
675.625, 163.5
33.059281786368935, 40.4807532077987

G-CSF: GCSFR

--

e44

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p42

p43 p44 p46 p45 p47 p66

true true true true

csml-variable:Double

m44

0

false

infinite

0

unit false false false

--

Go back
591.0, 511.0
34.0, 34.0

MAPK {activated}

--

e45

cso30:c:Protein

cso30:i:CC_CellComponent

--

p46

--

true true true true

csml-variable:Double

m45

10

false

infinite

0

unit false false false
TRANSPATHMO000016894

--

Go back
747.875, 145.5
32.25, 45.0

G-CSF: GCSFR: SOCS-3

--

e46

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p45

p44

true true true true

csml-variable:Double

m46

0

false

infinite

0

unit false false false

--

Go back
788.5, 1173.0
37.214532871972324, 19.847750865051903

AIR

--

e47

cso30:c:mRNA

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p49

--

true true true true

csml-variable:Double

m47

0

false

infinite

0

unit false false false

--

Go back
228.875, 1022.5
32.25, 45.0

IL-6: IL-6R: gp130: STAT3

--

e48

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p51

p22

true true true true

csml-variable:Double

m48

0

false

infinite

0

unit false false false

--

Go back
227.875, 1077.5
32.25, 45.0

IL-6: IL-6R: gp130: STAT3

--

e49

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p22

p53

true true true true

csml-variable:Double

m49

0

false

infinite

0

unit false false false

--

Go back
406.5, 143.0
33.425307557117755, 51.42355008787346

cytokine receptor: Jak1: Jak2

--

e5

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p3

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
455.7106940240049, 827.7317613634326
490.774763027727, 463.02901911246073

--

e50

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelopeLumen

--

--

--

true true true true

csml-variable:Double

m50

0

false

infinite

0

unit false true false

--

Go back
508.71802410893616, 838.7048759780839
286.9707180460081, 448.7673450124878

--

e51

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearPore

--

--

--

true true true true

csml-variable:Double

m51

0

false

infinite

0

unit false true false

--

Go back
462.10813041356573, 833.9118201400873
477.97989024860584, 450.6689015591505

--

e52

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearInnerMembrane

--

--

--

true true true true

csml-variable:Double

m52

0

false

infinite

0

unit false true false

--

Go back
463.0220498977884, 834.8625984134192
476.1520512801596, 448.7673450124878

--

e53

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearLumen

--

--

--

true true true true

csml-variable:Double

m53

0

false

infinite

0

unit false true false

--

Go back
455.7106940240049, 827.7317613634326
490.774763027727, 463.02901911246073

--

e54

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearOuterMembrane

--

--

--

true true true true

csml-variable:Double

m54

0

false

infinite

0

unit false true false

--

Go back
455.7106940240049, 827.7317613634326
490.774763027727, 463.02901911246073

--

e55

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleus

--

--

--

true true true true

csml-variable:Double

m55

0

false

infinite

0

unit false true false

--

Go back
463.0220498977884, 834.8625984134192
476.1520512801596, 448.7673450124878

--

e56

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleoplasm

--

--

--

true true true true

csml-variable:Double

m56

0

false

infinite

0

unit false true false

--

Go back
813.9671318394032, 1017.8874160297414
30.660910630037577, 28.875612679268418

--

e57

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearBody

--

--

--

true true true true

csml-variable:Double

m57

0

false

infinite

0

unit false true false

--

Go back
733.5422172277836, 1150.9963742961572
86.82235100118072, 81.76693150651265

--

e58

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleolus

--

--

--

true true true true

csml-variable:Double

m58

0

false

infinite

0

unit false true false

--

Go back
455.7106940240049, 827.7317613634326
490.774763027727, 463.02901911246073

--

e59

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelope

--

--

--

true true true true

csml-variable:Double

m59

0

false

infinite

0

unit false true false

--

Go back
336.375, 153.5
28.37475334356502, 54.918877439158095

cytokine: cytokine receptor: Jak1: Jak2

--

e6

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p3

p1

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
571.3835442701202, 1033.4980314167285
15.542115627322849, 7.785043370163178

--

e60

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Chromatin

--

--

--

true true true true

csml-variable:Double

m60

0

false

infinite

0

unit false true false

--

Go back
570.8645490360973, 1010.2811898430892
53.19701148731731, 99.61644814735934

--

e61

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearChromosome

--

--

--

true true true true

csml-variable:Double

m61

0

false

infinite

0

unit false true false

--

Go back
593.1813440990702, 1075.0723756299903
8.303923744361711, 8.63882477158671

--

e62

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearCentromere

--

--

--

true true true true

csml-variable:Double

m62

0

false

infinite

0

unit false true false

--

Go back
233.875, 1204.5
28.31221325013764, 39.50541383740136

IL23: IL23R: gp130: STAT3

--

e63

cso30:c:Complex

cso30:i:CC_Extracellular

--

p52

p23

true true true true

csml-variable:Double

m63

0

false

infinite

0

unit false false false

--

Go back
234.875, 1249.5
26.489309965131216, 36.96182785832263

IL23: IL23R: gp130: STAT3{activated}

--

e64

cso30:c:Complex

cso30:i:CC_Extracellular

--

p23

p54

true true true true

csml-variable:Double

m64

0

false

infinite

0

unit false false false

--

Go back
511.875, 1337.5
32.25, 45.0

IL-6: IL-6R: gp130: SOCS3

--

e65

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p55

p51

true true true true

csml-variable:Double

m65

0

false

infinite

0

unit false false false

--

Go back
663.875, 1337.5
32.25, 45.0

IL23: IL23R: gp130: SOCS3

--

e66

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p56

p52

true true true true

csml-variable:Double

m66

0

false

infinite

0

unit false false false

--

Go back
387.5, 1352.0
33.387935344109316, 40.88318613564406

IL-10: IL-10R

--

e67

cso30:c:Complex

cso30:i:CC_Extracellular

--

--

p50

true true true true

csml-variable:Double

m67

0

false

infinite

0

unit false false false

--

Go back
665.0, 1222.0
37.993079584775096, 20.26297577854671

S1008A

--

e68

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p57

--

true true true true

csml-variable:Double

m68

0

false

infinite

0

unit false false false

--

Go back
1036.375, 953.5
23.25, 45.0

TLR ligand: TLR

--

e69

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p59 p60 p67

true true true true

csml-variable:Double

m69

0

false

infinite

0

unit false false false

--

Go back
239.33522010824595, 147.42611402284157
821.6338354908867, 1211.1880062791145

--

e7

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell

--

--

--

true true true true

csml-variable:Double

m7

0

false

infinite

0

unit false true false

--

Go back
714.5, 671.125
34.28, 25.709999999999997

MAL {p}

--

e70

cso30:c:Protein

cso30:i:CC_Cytosol

--

p62

p61

true true true true

csml-variable:Double

m70

0

false

infinite

0

unit false false false

--

Go back
621.625, 725.5
29.499208465255787, 36.12147975337444

MAL{p}: SOSC-1

--

e71

cso30:c:Complex

cso30:i:CC_Cytosol

--

p61

p63

true true true true

csml-variable:Double

m71

0

false

infinite

0

unit false false false

--

Go back
805.0, 505.0
30.0, 30.0

CXCR4 {activated}

--

e72

cso30:c:Protein

cso30:i:CC_CellComponent

--

p64

--

true true true true

csml-variable:Double

m72

10

false

infinite

0

unit false false false
InterProIPR000276
TRANSPATHMO000017157

--

Go back
949.5, 559.125
36.2, 27.149999999999995

FAK {p}

--

e73

cso30:c:Protein

cso30:i:CC_Cytosol

--

p65

--

true true true true

csml-variable:Double

m73

0

false

infinite

0

unit false false false

--

Go back
968.0, 855.0
24.0, 24.0

p38 {activated}

--

e74

cso30:c:Protein

cso30:i:CC_CellComponent

--

p67

p69

true true true true

csml-variable:Double

m75

10

false

infinite

0

unit false false false
TRANSPATHMO000000022

--

Go back
1235.5, 749.375
33.99824253075571, 22.098857644991213

zymosan

--

e75

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p70

true true true true

csml-variable:Double

m77

0

false

infinite

0

unit false false false

--

Go back
961.0, 745.0
30.0, 30.0

ERK {activated}

--

e76

cso30:c:Protein

cso30:i:CC_CellComponent

--

p70

p68

true true true true

csml-variable:Double

m78

10

false

infinite

0

unit false false false
TRANSPATHMO000000011

--

Go back
900.0, 652.0
32.0, 32.0

STAT1 {activated}

--

e77

cso30:c:Protein

cso30:i:CC_CellComponent

--

p71

p72

true true true true

csml-variable:Double

m79

10

false

infinite

0

unit false false false
InterProIPR008967
TRANSPATHMO000013119

--

Go back
242.270592067233, 168.80241195336538
788.2031287865195, 1190.6279774601326

--

e8

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cell_WithoutCellWall_

--

--

--

true true true true

csml-variable:Double

m8

0

false

infinite

0

unit false true false

--

Go back
250.0982506245317, 190.1787098838892
784.604549147084, 1175.0131898801192

--

e9

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytoplasm

--

--

--

true true true true

csml-variable:Double

m9

0

false

infinite

0

unit false true false

--

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237.0, 89.0
30.0, 30.0

p1

p1

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e6

e11

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c5 : 1

m6*0.1

nodelay

--

true

0

false

PMID: 18400190 Upon cytokine binding to their cognate receptor, the receptor-associated Jaks are activated and in turn phosphorylate tyrosine residues in the receptor cytoplasmic domain.

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302.0, 710.0
27.0, 27.0

p10

p10

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000013133 e18 MO000017004

e22

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c24 : 1
stoichiometry:c27 : 1
stoichiometry:c150 : 1
stoichiometry:c25 : 1

m1371*m18*0.1

nodelay

--

true

0

false

PMID: 18400190, 16418296 IL-7 activates Stat5a and Stat5b, and deletion of the locus encoding Stat5a and Stat5b also results in a severe SCID phenotype. PMID: 18400190 Socs3 is an important inhibitor of cytokines that use gp130 (IL-23R and IL-6R), whereas Socs1 is anticipated to inhibit any cytokines that use gamma-c (IL-7, IL-21 as shown).

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138.0, 634.0
27.0, 27.0

p11

p11

cso30:i:CE_CellDifferentiation

cso30:i:CC_Extracellular

--

e20 MO000000147 MO000017004

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c28 : 1
stoichiometry:c49 : 1
stoichiometry:c172 : 1

m20*m131*0.1

nodelay

--

true

0

false

PMID: 18400190 Stat5 signaling from cytokines that use ¦Ãc is essential for T cell development. PMID: 18400190, 16455959 Deficiency of gamma-c or Jak3 causes a failure to produce Foxp3-positive regulatory T cells. PMID: 18400190 On one hand, Socs1 regulates T cell development by inhibiting gamma-c signaling.

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751.0, 903.0
25.0, 25.0

p12

p12

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e27

G011587

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c46 : 1
stoichiometry:c30 : 1

m27*0.1

nodelay

--

true

0

false

PMID: 18400190 Stat5 signaling controls the development of FoxP3-positive Treg cells in part through the direct activation of Foxp3 gene expression. PMID: 18400190 Stat5 appears to have very direct effects on Treg cells in that these transcription factors bind directly to the Foxp3 gene.

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262.0, 809.0
25.0, 25.0

p13

p13

cso30:i:ME_UnknownActivation

cso30:i:CC_Extracellular

--

MO000017181 MO000017265

e23

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c31 : 1
stoichiometry:c35 : 1
stoichiometry:c32 : 1

m2053*m2121*0.1

nodelay

--

true

0

false

PMID: 18400190 IL-12 activates Stat4, whereas IL-4 activates Stat6.

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267.0, 888.0
25.0, 25.0

p14

p14

cso30:i:ME_UnknownActivation

cso30:i:CC_Extracellular

--

MO000013130 MO000017053

e24

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c33 : 1
stoichiometry:c36 : 1
stoichiometry:c34 : 1

m1368*m1947*0.1

nodelay

--

true

0

false

PMID: 18400190 IL-12 activates Stat4, whereas IL-4 activates Stat6.

Go back
87.0, 849.0
25.0, 25.0

p15

p15

cso30:i:CE_CellDifferentiation

cso30:i:CC_Extracellular

--

e23

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c37 : 1

m23*0.1

nodelay

--

true

0

false

PMID: 18400190 These fates are driven by the cytokine milieu with IL-12 driving Th1 cell differentiation and IL-4 promoting Th2 cell differentiation. PMID: 18400190, 11121747 Stat4- and Stat6-deficient mice have impaired Th1 and Th2 cell responses, respectively. PMID: 18400190, 12242445 Depending upon the circumstance, type I IFN signaling may enhance or inhibit Th1 cell responses.

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87.0, 924.0
27.0, 27.0

p16

p16

cso30:i:CE_CellDifferentiation

cso30:i:CC_Extracellular

--

e24

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c38 : 1

m24*0.1

nodelay

--

true

0

false

PMID: 18400190 These fates are driven by the cytokine milieu with IL-12 driving Th1 cell differentiation and IL-4 promoting Th2 cell differentiation. PMID: 18400190, 11121747 Stat4- and Stat6-deficient mice have impaired Th1 and Th2 cell responses, respectively.

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386.0, 790.0
27.0, 27.0

p17

p17

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000017181 MO000016658

e23

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c39 : 1
stoichiometry:c41 : 1
stoichiometry:c40 : 1

m2053*m1634*0.1

nodelay

--

true

0

false

PMID: 18400190 In this regard, it is important to note that type I IFNs also activate Stat4.

Go back
559.0, 783.0
25.0, 25.0

p18

p18

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

e20

e25

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c29 : 1
stoichiometry:c42 : 1

m20*0.1

nodelay

--

true

0

false

PMID: 18400190 Stat5 appears to have very direct effects on Treg cells in that these transcription factors bind directly to the Foxp3 gene.

Go back
619.0, 871.0
23.0, 23.0

p19

p19

cso30:i:ME_Binding

cso30:i:CC_Nucleoplasm

--

e25 e26

e27

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c43 : 1
stoichiometry:c44 : 1
stoichiometry:c45 : 1

m25*m26*0.1

nodelay

--

true

0

false

PMID: 18400190 Stat5 appears to have very direct effects on Treg cells in that these transcription factors bind directly to the Foxp3 gene.

Go back
143.0, 260.0
27.0, 27.0

p2

p2

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e11

e12

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c6 : 1
stoichiometry:c7 : 1

m11*0.1

nodelay

--

true

0

false

PMID: 18400190 Upon cytokine binding to their cognate receptor, the receptor-associated Jaks are activated and in turn phosphorylate tyrosine residues in the receptor cytoplasmic domain.

Go back
141.0, 709.0
30.0, 30.0

p20

p20

cso30:i:CE_CellDifferentiation

cso30:i:CC_Extracellular

--

e21 e22

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c47 : 1
stoichiometry:c48 : 1

m21*m22*0.1

nodelay

--

true

0

false

PMID: 18400190, 17227828 Accordingly, deficiency of both Stat5a and Stat5b also leads to loss of Treg cells and inability to induce Treg cells in vitro. PMID: 18400190 In both cases, cytokines that use gamma-c are important drivers of Treg cell development.

Go back
474.0, 1242.0
27.0, 27.0

p21

p21

cso30:i:ME_Translation

cso30:i:CC_Nucleoplasm

--

G011341 e30 MO000017004

MO000007327

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c60 : 1
stoichiometry:c61 : 1
stoichiometry:c152 : 1
stoichiometry:c51 : 1

m94226*m30*0.1

nodelay

--

true

0

false

PMID: 18400190, 17581589, 17581537 Th17 cells can be generated from naive CD4+ T cells by IL-6 and TGF-beta but can also produce another cytokine IL-21, which promotes IL-17 production in an autocrine-paracrine manner.

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303.0, 1067.0
27.0, 27.0

p22

p22

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e48

e49

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c53 : 1
stoichiometry:c54 : 1

m48*0.1

nodelay

--

true

0

false

PMID: 18400190 IL-6, IL-21, and IL-23 all activate Stat3 via their cognate receptors.

Go back
294.0, 1210.0
27.0, 27.0

p23

p23

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e63

e64

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c132 : 1
stoichiometry:c133 : 1

m63*0.1

nodelay

--

true

0

false

PMID: 18400190 IL-6, IL-21, and IL-23 all activate Stat3 via their cognate receptors.

Go back
298.0, 1258.0
27.0, 27.0

p24

p24

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000013122 e30 MO000017004

e28

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c55 : 1
stoichiometry:c59 : 1
stoichiometry:c151 : 1
stoichiometry:c56 : 1

m1360*m30*0.1

nodelay

--

true

0

false

PMID: 18400190 IL-6, IL-21, and IL-23 all activate Stat3 via their cognate receptors.

Go back
680.0, 1098.0
23.0, 23.0

p25

p25

cso30:i:ME_Binding

cso30:i:CC_Nucleoplasm

--

e31 e32

e34

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c64 : 1
stoichiometry:c68 : 1
stoichiometry:c66 : 1

m31*m32*0.1

nodelay

--

true

0

false

PMID: 18400190, 16698929, 17884812 However, Stat3 also directly regulates the expression of Il21 and Il17.

Go back
544.0, 1104.0
24.0, 24.0

p26

p26

cso30:i:ME_Binding

cso30:i:CC_Nucleoplasm

--

e31 e33

e35

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c65 : 1
stoichiometry:c69 : 1
stoichiometry:c67 : 1

m31*m33*0.1

nodelay

--

true

0

false

PMID: 18400190, 16698929, 17884812 However, Stat3 also directly regulates the expression of Il21 and Il17.

Go back
443.0, 1151.0
25.0, 25.0

p27

p27

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

e28

e31

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c62 : 1
stoichiometry:c63 : 1

m28*0.1

nodelay

--

true

0

false

PMID: 18400190, 16698929, 17884812 However, Stat3 also directly regulates the expression of Il21 and Il17.

Go back
806.0, 1096.0
27.0, 27.0

p28

p28

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e34

G011174

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c70 : 1
stoichiometry:c71 : 1

m34*0.1

nodelay

--

true

0

false

PMID: 18400190, 16698929, 17884812 However, Stat3 also directly regulates the expression of Il21 and Il17.

Go back
646.0, 1178.0
27.0, 27.0

p29

p29

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleolus

--

e35

G011341

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c73 : 1
stoichiometry:c72 : 1

m35*0.1

nodelay

--

true

0

false

PMID: 18400190, 16698929, 17884812 However, Stat3 also directly regulates the expression of Il21 and Il17.

Go back
338.0, 80.0
25.0, 25.0

p3

p3

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e5 MO000019387

e6

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c2 : 1
stoichiometry:c3 : 1

m5*m3957*0.1

nodelay

--

true

0

false

PMID: 18400190 Upon cytokine binding to their cognate receptor, the receptor-associated Jaks are activated and in turn phosphorylate tyrosine residues in the receptor cytoplasmic domain.

Go back
680.0, 1030.0
23.0, 23.0

p30

p30

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e31

e36

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c74 : 1
stoichiometry:c76 : 1

m31*0.1

nodelay

--

true

0

false

PMID: 18400190, 18164222 Accordingly, selective deletion of Stat3 in T cells abrogates Th17 cell differentiation in part because the expression of RORgammat and RORalpha, two nuclear hormone receptors essential for Th17 cell development, is also abrogated. PMID: 18400190 IL-23 and IL-6 enforce Th17 cell development via the direct or indirect induction of Rorc and Rora expression.

Go back
679.0, 1061.0
25.0, 25.0

p31

p31

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e31

G011523

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c75 : 1
stoichiometry:c77 : 1

m31*0.1

nodelay

--

true

0

false

PMID: 18400190, 18164222 Accordingly, selective deletion of Stat3 in T cells abrogates Th17 cell differentiation in part because the expression of RORgammat and RORalpha, two nuclear hormone receptors essential for Th17 cell development, is also abrogated. PMID: 18400190 IL-23 and IL-6 enforce Th17 cell development via the direct or indirect induction of Rorc and Rora expression.

Go back
1153.0, 1037.0
30.0, 30.0

p32

p32

cso30:i:CE_CellDifferentiation

cso30:i:CC_Extracellular

--

e36 G011523 e20

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c78 : 1
stoichiometry:c79 : 1
stoichiometry:c83 : 1

m36*m94396*0.1

nodelay

--

true

0

false

PMID: 18400190, 18164222 Accordingly, selective deletion of Stat3 in T cells abrogates Th17 cell differentiation in part because the expression of RORgammat and RORalpha, two nuclear hormone receptors essential for Th17 cell development, is also abrogated. PMID: 18400190 IL-23 and IL-6 enforce Th17 cell development via the direct or indirect induction of Rorc and Rora expression. PMID: 18400190, 17363300 Parenthetically, it is interesting to note that IL-2 acting through Stat5 inhibits Th17 cell differentiation.

Go back
430.0, 538.0
27.0, 27.0

p33

p33

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000016876 MO000017061

e20

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c80 : 1
stoichiometry:c82 : 1
stoichiometry:c81 : 1

m1798*m1954*0.1

nodelay

--

true

0

false

PMID: 18400190, 17363300 Parenthetically, it is interesting to note that IL-2 acting through Stat5 inhibits Th17 cell differentiation.

Go back
90.0, 982.0
27.0, 27.0

p34

p34

cso30:i:CE_CellDifferentiation

cso30:i:CC_Extracellular

--

e19 MO000017443

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c84 : 1
stoichiometry:c85 : 1

m19*m2269*0.1

nodelay

--

true

0

false

PMID: 18400190 whereas IL-6 and TGF-beta-1 are important for the differentiation of Th17 cells, IL-6 alone so far appears to be capable of inducing IL-22.

Go back
491.0, 1003.0
25.0, 25.0

p35

p35

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e19

G011175

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c86 : 1
stoichiometry:c87 : 1

m19*0.1

nodelay

--

true

0

false

PMID: 18400190 whereas IL-6 and TGF-beta-1 are important for the differentiation of Th17 cells, IL-6 alone so far appears to be capable of inducing IL-22.

Go back
315.0, 1287.0
25.0, 25.0

p36

p36

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000013122 MO000019517

e28

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c88 : 1
stoichiometry:c90 : 1
stoichiometry:c89 : 1

m1360*m4068*0.1

nodelay

--

true

0

false

PMID: 18400190 An additional complexity of Th17 T cells in inflammation concerns the Stat3-activating cytokine IL-22.

Go back
643.0, 935.0
25.0, 25.0

p37

p37

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e15

e37

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c92 : 1
stoichiometry:c91 : 1

m15*0.1

nodelay

--

true

0

false

PMID: 18400190 Importantly, the genes encoding the Socs proteins are direct targets of Stat proteins; the Jak-Stat cascades thereby control their own signaling output by feedback inhibition.

Go back
540.0, 314.0
27.0, 27.0

p38

p38

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e38 e39 MO000018947 MO000018946 e41

e40

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c93 : 1
stoichiometry:c94 : 1
stoichiometry:c95 : 1
stoichiometry:c96 : 1
stoichiometry:c98 : 1
stoichiometry:c97 : 1

m38*m39*m3559*m3558*m41*0.1

nodelay

--

true

0

false

PMID: 18400190, 12076535, 10051596 Each of the eight Socs proteins have two major domains, an SH2 domain and a Socs box that complexes with elongins B and C, a cullin and Rbx2, to form a E3 ubiquitin ligase.

Go back
328.0, 313.0
25.0, 25.0

p39

p39

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e40 e13

e42

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c99 : 1
stoichiometry:c100 : 1
stoichiometry:c101 : 1

m40*m13*0.1

nodelay

--

true

0

false

PMID: 18400190 The Socs SH2 domains bind phosphorylated tyrosine residues in their substrates. The best characterized Socs substrates are specific tyrosine residues in the cytoplasmic tails of cytokine receptors.

Go back
328.0, 261.0
25.0, 25.0

p4

p4

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e12 MO000016656

e13

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c8 : 1
stoichiometry:c9 : 1
stoichiometry:c10 : 1

m12*m1633*0.1

nodelay

--

true

0

false

PMID: 18400190 This event provides a docking site for proteins with Src homology 2 domains, one important class of which is the Stat family of transcription factors.

Go back
323.0, 364.0
27.0, 27.0

p40

p40

cso30:i:ME_Ubiquitination

cso30:i:CC_Cytosol

--

e42

e43

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c102 : 1
stoichiometry:c103 : 1

m42*0.1

nodelay

--

true

0

false

PMID: 18400190 The current model of Socs function postulates that the E3 activity of a Socs protein will target the substrate to be ubiquitinated and then directed to the proteosome for degradation.

Go back
324.0, 417.0
26.0, 26.0

p41

p41

cso30:i:ME_ProteasomeDegradation

cso30:i:CC_Cytosol

--

e43

MO000019479

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c104 : 1
stoichiometry:c105 : 1

m43*0.1

nodelay

--

true

0

false

PMID: 18400190 The current model of Socs function postulates that the E3 activity of a Socs protein will target the substrate to be ubiquitinated and then directed to the proteosome for degradation.

Go back
678.0, 80.0
27.0, 27.0

p42

p42

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000003473 MO000089770

e44

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c106 : 1
stoichiometry:c107 : 1
stoichiometry:c108 : 1

m464*m63352*0.1

nodelay

--

true

0

false

PMID: 18400190 The G-CSFR is responsible for transducing the signals from G-CSF via four tyrosine residues located in the cytoplasmic tail of the receptor.

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470.0, 566.0
27.0, 27.0

p43

p43

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000016876 e44

e20

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c109 : 1
stoichiometry:c111 : 1
stoichiometry:c110 : 1

m1798*m44*0.1

nodelay

--

true

0

false

PMID: 18400190 G-CSFR signaling via the cytoplasmic tyrosines activates numerous signaling molecules including Stat5, Stat3, and MAP kinases.

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362.0, 1294.0
27.0, 27.0

p44

p44

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000013122 e44 e46

e28

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c112 : 1
stoichiometry:c114 : 1
stoichiometry:c121 : 1
stoichiometry:c113 : 1

m1360*m44*0.1

nodelay

--

true

0

false

PMID: 18400190 G-CSFR signaling via the cytoplasmic tyrosines activates numerous signaling molecules including Stat5, Stat3, and MAP kinases. PMID: 18400190, 12133942 Indeed, Socs3 binds to one of the tyrosine residues in the G-CSFR (Y729) and restricts the amplitude of Stat3 signaling.

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751.0, 231.0
25.0, 25.0

p45

p45

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e44 MO000017121

e46

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c118 : 1
stoichiometry:c119 : 1
stoichiometry:c120 : 1

m44*m2005*0.1

nodelay

--

true

0

false

PMID: 18400190, 12133942 Indeed, Socs3 binds to one of the tyrosine residues in the G-CSFR (Y729) and restricts the amplitude of Stat3 signaling.

Go back
655.0, 515.0
25.0, 25.0

p46

p46

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e44 MO000016894

e45

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c115 : 1
stoichiometry:c116 : 1
stoichiometry:c117 : 1

m44*m1812*0.1

nodelay

--

true

0

false

PMID: 18400190 G-CSFR signaling via the cytoplasmic tyrosines activates numerous signaling molecules including Stat5, Stat3, and MAP kinases.

Go back
798.0, 68.0
27.0, 27.0

p47

p47

cso30:i:CE_CellProliferation

cso30:i:CC_Extracellular

--

e44

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c122 : 1

m44*0.1

nodelay

--

true

0

false

PMID: 18400190 Thus, loss of Socs3 causes increased G-CSFR signaling leading to increased neutrophil numbers, whereas loss of Stat3 (and failure to induce Socs3 expression) also leads to increased neutrophil numbers.

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729.0, 1133.0
27.0, 27.0

p48

p48

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleolus

--

e31

G011948

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c124 : 1
stoichiometry:c123 : 1

m31*0.1

nodelay

--

true

0

false

PMID: 18400190 Thus, loss of Socs3 causes increased G-CSFR signaling leading to increased neutrophil numbers, whereas loss of Stat3 (and failure to induce Socs3 expression) also leads to increased neutrophil numbers. PMID: 18400190 Socs3 expression is strongly induced by IL-10, along with the Stat3-dependent genes whose products regulate the anti-inflammatory signaling system (¡Èanti-inflammatory response¡É AIR gene whose identity has yet to be determined) illustrated as inhibiting the expression at the transcriptional level of classic pro-inflammatory genes.

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730.0, 1170.0
25.0, 25.0

p49

p49

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleolus

--

e31

e47

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c129 : 1
stoichiometry:c125 : 1

m31*0.1

nodelay

--

true

0

false

PMID: 18400190 Socs3 expression is strongly induced by IL-10, along with the Stat3-dependent genes whose products regulate the anti-inflammatory signaling system (¡Èanti-inflammatory response¡É AIR gene whose identity has yet to be determined) illustrated as inhibiting the expression at the transcriptional level of classic pro-inflammatory genes.

Go back
394.0, 750.0
27.0, 27.0

p5

p5

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

MO000016656

e14

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c11 : 1
stoichiometry:c12 : 1

m1633*0.1

nodelay

--

true

0

false

PMID: 18400190, 14668806 With seven members in all (Stat1, Stat2, Stat3, Stat4, Stat5a, Stat5b, and Stat6), these DNA-binding proteins provide a rapid membrane to nucleus mechanism for regulation of gene expression.

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391.0, 1291.0
25.0, 25.0

p50

p50

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000013122 e67

e28

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c126 : 1
stoichiometry:c139 : 1
stoichiometry:c127 : 1

m1360*m67*0.1

nodelay

--

true

0

false

PMID: 18400190 Socs3 expression is strongly induced by IL-10, along with the Stat3-dependent genes whose products regulate the anti-inflammatory signaling system (¡Èanti-inflammatory response¡É AIR gene whose identity has yet to be determined) illustrated as inhibiting the expression at the transcriptional level of classic pro-inflammatory genes.

Go back
304.0, 1032.0
25.0, 25.0

p51

p51

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

e19 MO000013122 e65

e48

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c50 : 1
stoichiometry:c57 : 1
stoichiometry:c146 : 1
stoichiometry:c52 : 1

m19*m1360*0.1

nodelay

--

true

0

false

PMID: 18400190 Gp130 has multiple tyrosine residues in its cytoplasmic tail, all of which bar one, Y757, serve as docking sites for Stat proteins (especially Stat3) PMID: 18400190 Socs3 is an important inhibitor of cytokines that use gp130 (IL-23R and IL-6R), whereas Socs1 is anticipated to inhibit any cytokines that use gamma-c (IL-7, IL-21 as shown).

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295.0, 1179.0
25.0, 25.0

p52

p52

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e29 MO000013122 e66

e63

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c58 : 1
stoichiometry:c130 : 1
stoichiometry:c147 : 1
stoichiometry:c131 : 1

m29*m1360*0.1

nodelay

--

true

0

false

PMID: 18400190 Gp130 has multiple tyrosine residues in its cytoplasmic tail, all of which bar one, Y757, serve as docking sites for Stat proteins (especially Stat3) PMID: 18400190 Socs3 is an important inhibitor of cytokines that use gp130 (IL-23R and IL-6R), whereas Socs1 is anticipated to inhibit any cytokines that use gamma-c (IL-7, IL-21 as shown).

Go back
421.0, 1089.0
23.0, 23.0

p53

p53

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

e49

e31 e19

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c134 : 1
stoichiometry:c135 : 1
stoichiometry:c136 : 1

m49*0.1

nodelay

--

true

0

false

PMID: 18400190, 16698929, 17884812 However, Stat3 also directly regulates the expression of Il21 and Il17.

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415.0, 1151.0
26.0, 26.0

p54

p54

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

e64

e31 e29

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c137 : 1
stoichiometry:c138 : 1
stoichiometry:c128 : 1

m64*0.1

nodelay

--

true

0

false

PMID: 18400190, 16698929, 17884812 However, Stat3 also directly regulates the expression of Il21 and Il17.

Go back
567.0, 1255.0
25.0, 25.0

p55

p55

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e19 MO000017121

e65

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c140 : 1
stoichiometry:c144 : 1
stoichiometry:c142 : 1

m19*m2005*0.1

nodelay

--

true

0

false

PMID: 18400190, 16678769, 12687404 Y757 docks the SH2 domain of Socs3 and is by far the best-characterized Socs-cytokine receptor interaction.

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623.0, 1283.0
25.0, 25.0

p56

p56

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e29 MO000017121

e66

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c141 : 1
stoichiometry:c145 : 1
stoichiometry:c143 : 1

m29*m2005*0.1

nodelay

--

true

0

false

PMID: 18400190, 16678769, 12687404 Y757 docks the SH2 domain of Socs3 and is by far the best-characterized Socs-cytokine receptor interaction.

Go back
733.0, 1221.0
22.0, 22.0

p57

p57

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

MO000019517

e68

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c154 : 1
stoichiometry:c153 : 1

m4068*0.1

nodelay

--

true

0

false

PMID: 18400190, 18276893 IL-22 induces the expression of antimicrobial proteins, including S1008A, a zinc and manganese chelating protein that deprives bacteria of essential cations.

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663.0, 843.0
25.0, 25.0

p58

p58

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

MO000017053

G010539

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c156 : 1
stoichiometry:c155 : 1

m1947*0.1

nodelay

--

true

0

false

PMID: 18400190 Socs1, unlike the broad expression of Socs3, is activated predominantly by interferon signaling, although other cytokines such as IL-4 also activate Socs1 expression but in a cell-type-dependent way.

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967.0, 963.0
26.0, 26.0

p59

p59

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e69 G016992

MO000016659

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c158 : 1
stoichiometry:c159 : 1
stoichiometry:c157 : 1

m69*m98717*0.1

nodelay

--

true

0

false

PMID: 18400190 Because TLR signaling induces autocrine-paracrine IFN-alpha-beta production, this might underlie the cause of LPS sensitivity in Socs1¡Ý/¡Ý; Ifng¡Ý/¡Ý mice.

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578.0, 915.0
25.0, 25.0

p6

p6

cso30:i:ME_Binding

cso30:i:CC_Nucleoplasm

--

e14 e16

e15

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c13 : 1
stoichiometry:c14 : 1
stoichiometry:c15 : 1

m14*m16*0.1

nodelay

--

true

0

false

PMID: 18400190, 14668806 With seven members in all (Stat1, Stat2, Stat3, Stat4, Stat5a, Stat5b, and Stat6), these DNA-binding proteins provide a rapid membrane to nucleus mechanism for regulation of gene expression.

Go back
967.0, 1003.0
25.0, 25.0

p60

p60

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G010228 e69

MO000016660

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c161 : 1
stoichiometry:c162 : 1
stoichiometry:c160 : 1

m93217*m69*0.1

nodelay

--

true

0

false

PMID: 18400190 Because TLR signaling induces autocrine-paracrine IFN-alpha-beta production, this might underlie the cause of LPS sensitivity in Socs1¡Ý/¡Ý; Ifng¡Ý/¡Ý mice.

Go back
624.0, 672.0
23.0, 23.0

p61

p61

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e70 MO000017004

e71

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c166 : 1
stoichiometry:c167 : 1
stoichiometry:c168 : 1

m70*m1906*0.1

nodelay

--

true

0

false

PMID: 18400190, 16415872 Mansell et al. have demonstrated that Socs1 can bind to and regulate the degradation of Mal (also known as TIRAP), an adaptor molecule specifically associated with TLR2 and TLR4 signaling.

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718.0, 611.0
25.0, 25.0

p62

p62

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

MO000001935 MO000068831

e70

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c163 : 1
stoichiometry:c164 : 1
stoichiometry:c165 : 1

m367*m43675*0.1

nodelay

--

true

0

false

PMID: 18400190, 16439361 Previous studies had shown that the tyrosine kinase Btk phosphorylates Mal, providing binding sites for Socs1.

Go back
519.0, 731.0
25.0, 25.0

p63

p63

cso30:i:ME_ProteasomeDegradation

cso30:i:CC_Cytosol

--

e71

MO000019479 MO000017004

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c169 : 1
stoichiometry:c170 : 1
stoichiometry:c171 : 1

m71*0.1

nodelay

--

true

0

false

PMID: 18400190, 16415872 Mansell et al. have demonstrated that Socs1 can bind to and regulate the degradation of Mal (also known as TIRAP), an adaptor molecule specifically associated with TLR2 and TLR4 signaling.

Go back
882.0, 458.0
27.0, 27.0

p64

p64

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000017157 MO000019001 e28

e72

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c173 : 1
stoichiometry:c175 : 1
stoichiometry:c179 : 1
stoichiometry:c174 : 1

m2033*m3609*0.1

nodelay

--

true

0

false

PMID: 18400190 The chemokine CXCL12 activates CXCR4 and induces phosphorylation of FAK, a ubiquitous tyrosine kinase, in addition to other pathways. PMID: 18400190, 12163560 Therefore, the assignment of FAK as a substrate of Socs3 potentially explains previous data that suggested that Socs3 directly regulates CXCR4 to inhibit its activity.

Go back
883.0, 507.0
25.0, 25.0

p65

p65

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

MO000016855 MO000019001 e28

e73

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c176 : 1
stoichiometry:c178 : 1
stoichiometry:c182 : 1
stoichiometry:c177 : 1

m1787*m3609*0.1

nodelay

--

true

0

false

PMID: 18400190 The chemokine CXCL12 activates CXCR4 and induces phosphorylation of FAK, a ubiquitous tyrosine kinase, in addition to other pathways. PMID: 18400190 Le et al. have shown that Socs3 is crucial to regulate the amounts of CXCL12-activated phospho-FAK because Socs3-deficient B cells have increased amount of phospho-FAK.

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950.0, 398.0
27.0, 27.0

p66

p66

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

e44

MO000019001

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c180 : 1
stoichiometry:c181 : 1

1.0*0.1

nodelay

--

true

0

false

PMID: 18400190, 12387736 Link and colleagues have also postulated that signals from the G-CSFR negatively regulate CXCL12 amounts in the bone marrow, thereby allowing escape of neutrophils into the circulation.

Go back
1086.0, 801.0
27.0, 27.0

p67

p67

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e69 MO000000022

e74

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c183 : 1
stoichiometry:c184 : 1
stoichiometry:c185 : 1

m69*m74*0.1

nodelay

--

true

0

false

PMID: 18400190 Addressing this question is complicated by the diversity of stimuli and downstream signaling molecules that contribute to myeloid IL-10 production including TLR agonists via TLRs and the p38 MAP kinase pathways and zymosan via the dectin and ERK pathways, to list a few.

Go back
870.0, 850.0
27.0, 27.0

p68

p68

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G011345 e76

MO000017247

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c189 : 1
stoichiometry:c194 : 1
stoichiometry:c187 : 1

m94230*m78*0.1

nodelay

--

true

0

false

PMID: 18400190 Addressing this question is complicated by the diversity of stimuli and downstream signaling molecules that contribute to myeloid IL-10 production including TLR agonists via TLRs and the p38 MAP kinase pathways and zymosan via the dectin and ERK pathways, to list a few.

Go back
911.0, 867.0
25.0, 25.0

p69

p69

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e74 G011345

MO000017247

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c186 : 1
stoichiometry:c190 : 1
stoichiometry:c188 : 1

m75*m94230*0.1

nodelay

--

true

0

false

PMID: 18400190 Addressing this question is complicated by the diversity of stimuli and downstream signaling molecules that contribute to myeloid IL-10 production including TLR agonists via TLRs and the p38 MAP kinase pathways and zymosan via the dectin and ERK pathways, to list a few.

Go back
139.0, 539.0
25.0, 25.0

p7

p7

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000016830 e17

e18

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c16 : 1
stoichiometry:c17 : 1
stoichiometry:c18 : 1

m1767*m17*0.1

nodelay

--

true

0

false

PMID: 18400190 As an example of the overall importance of cytokine-cytokine receptor-Jak-Stat pathway signaling in thymic T cell development, IL-7 signaling ensures development of appropriate lymphocyte numbers. PMID: 18400190 Stat5 signaling from cytokines that use ¦Ãc is essential for T cell development.

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1098.0, 746.0
27.0, 27.0

p70

p70

cso30:i:ME_UnknownActivation

cso30:i:CC_Extracellular

--

MO000000011 e75

e76

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c191 : 1
stoichiometry:c193 : 1
stoichiometry:c192 : 1

m76*m77*0.1

nodelay

--

true

0

false

PMID: 18400190 Addressing this question is complicated by the diversity of stimuli and downstream signaling molecules that contribute to myeloid IL-10 production including TLR agonists via TLRs and the p38 MAP kinase pathways and zymosan via the dectin and ERK pathways, to list a few.

Go back
966.0, 614.0
27.0, 27.0

p71

p71

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000013119 MO000062893

e77

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c195 : 1
stoichiometry:c197 : 1
stoichiometry:c196 : 1

m1357*m37778*0.1

nodelay

--

true

0

false

PMID: 18400190, 18400189 Aspects of this complex regulatory pathway including the role of IL-27 in driving IL-10 production via Stat1 and Stat3 are covered in the review by Li and Flavell, (2008).

Go back
843.0, 823.0
25.0, 25.0

p72

p72

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

G011345 e77

MO000017247

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c199 : 1
stoichiometry:c205 : 1
stoichiometry:c198 : 1

m94230*m79*0.1

nodelay

--

true

0

false

PMID: 18400190, 18400189 Aspects of this complex regulatory pathway including the role of IL-27 in driving IL-10 production via Stat1 and Stat3 are covered in the review by Li and Flavell, (2008).

Go back
433.0, 1293.0
23.0, 23.0

p73

p73

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000013122 MO000062893

e28

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c200 : 1
stoichiometry:c204 : 1
stoichiometry:c201 : 1

m1360*m37778*0.1

nodelay

--

true

0

false

PMID: 18400190, 18400189 Aspects of this complex regulatory pathway including the role of IL-27 in driving IL-10 production via Stat1 and Stat3 are covered in the review by Li and Flavell, (2008).

Go back
802.0, 810.0
27.0, 27.0

p74

p74

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e31

MO000017247

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c203 : 1
stoichiometry:c202 : 1

m31*0.1

nodelay

--

true

0

false

PMID: 18400190, 18400189 Aspects of this complex regulatory pathway including the role of IL-27 in driving IL-10 production via Stat1 and Stat3 are covered in the review by Li and Flavell, (2008).

Go back
307.0, 539.0
26.0, 26.0

p8

p8

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e18 MO000016876 MO000017004

e20

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c21 : 1
stoichiometry:c19 : 1
stoichiometry:c148 : 1
stoichiometry:c20 : 1

m18*m1798*0.1

nodelay

--

true

0

false

PMID: 18400190 Stat5 signaling from cytokines that use ¦Ãc is essential for T cell development. PMID: 18400190 Socs3 is an important inhibitor of cytokines that use gp130 (IL-23R and IL-6R), whereas Socs1 is anticipated to inhibit any cytokines that use gamma-c (IL-7, IL-21 as shown).

Go back
298.0, 630.0
27.0, 27.0

p9

p9

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000013126 e18 MO000017004

e21

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c22 : 1
stoichiometry:c26 : 1
stoichiometry:c149 : 1
stoichiometry:c23 : 1

m1364*m18*0.1

nodelay

--

true

0

false

PMID: 18400190, 16418296 IL-7 activates Stat5a and Stat5b, and deletion of the locus encoding Stat5a and Stat5b also results in a severe SCID phenotype. PMID: 18400190 Socs3 is an important inhibitor of cytokines that use gp130 (IL-23R and IL-6R), whereas Socs1 is anticipated to inhibit any cytokines that use gamma-c (IL-7, IL-21 as shown).

Go back
367.5325719930081, 110.77846408158624

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
279.8047565563683, 282.0

c10

c10

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
273.0, 326.0

c100

c100

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
275.88043723098957, 334.0

c101

c101

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
269.0, 378.0

c102

c102

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
275.8262546692157, 387.0

c103

c103

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
269.0, 430.0

c104

c104

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
350.0, 430.0

c105

c105

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
713.0, 94.0

c106

c106

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
633.0, 113.35204443655223

c107

c107

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
692.0, 107.0

c108

c108

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
392.0, 556.0

c109

c109

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
408.0173159767528, 288.0

c11

c11

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
399.87416965595105, 583.0

c110

c110

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
504.9999854544802, 204.0

c111

c111

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
377.3430318535677, 1061.0

c112

c112

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
389.0, 1242.9101281982717

c113

c113

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
44.15838508437281, 51.555737181623215

c114

c114

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
669.5645057442136, 204.0

c115

c115

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
621.0, 496.0

c116

c116

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
633.0, 528.0

c117

c117

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
709.0, 198.0

c118

c118

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
784.0, 244.0

c119

c119

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
418.0, 777.0

c12

c12

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
764.0, 199.0

c120

c120

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
24.20563939612208, 35.65050340119319

c121

c121

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
709.0, 99.19506339262138

c122

c122

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
756.0, 1147.0

c123

c123

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
529.0, 1077.0

c124

c124

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
755.0, 1183.0

c125

c125

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
389.0, 1061.0

c126

c126

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
412.0, 1243.8262546692156

c127

c127

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
272.0, 1164.0

c128

c128

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
529.0, 1080.0

c129

c129

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
553.0, 928.0

c13

c13

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
318.8141043230231, 1061.0

c130

c130

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
269.11179645141283, 1199.0

c131

c131

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
262.0, 1224.0

c132

c132

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
267.46988867442553, 1234.0

c133

c133

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
260.0, 1100.0

c134

c134

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
444.0, 1080.7928721853837

c135

c135

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
265.93802477467847, 1004.9829401484266

c136

c136

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
261.0, 1175.0029701019141

c137

c137

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
440.0, 1094.8893409368075

c138

c138

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
404.0, 1324.0

c139

c139

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
524.0, 936.0183750985082

c14

c14

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
156.0889465518831, 1002.0

c140

c140

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
183.82423377661564, 1164.0

c141

c141

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
544.8646187432906, 1280.0

c142

c142

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
644.0, 1308.0

c143

c143

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
599.9999998346352, 245.0

c144

c144

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
655.999999938295, 243.53131174719374

c145

c145

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
327.2242583345652, 1060.3245563404937

c146

c146

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
323.6429151783938, 1198.6520196739227

c147

c147

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
335.7863234607402, 567.8699131645624

c148

c148

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
328.84200458018967, 649.1131041307092

c149

c149

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
591.0, 940.0

c15

c15

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
332.8302801213651, 689.0

c150

c150

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
315.90096821443314, 700.0

c151

c151

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
449.0, 700.0

c152

c152

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
711.0, 1232.0

c153

c153

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
343.0, 1250.9999842399436

c154

c154

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
688.0, 859.0

c155

c155

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
186.0, 857.7182614562751

c156

c156

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
980.0, 942.0

c157

c157

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1001.0, 976.0

c158

c158

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
910.0, 976.0

c159

c159

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
105.0, 552.0

c16

c16

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
980.0, 1028.0

c160

c160

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
915.0, 1016.0

c161

c161

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
998.8874122257146, 983.0

c162

c162

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
751.0, 624.0

c163

c163

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
682.0, 624.0

c164

c164

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
731.0, 636.0

c165

c165

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
655.0, 684.0

c166

c166

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
464.0, 684.0

c167

c167

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
636.0, 695.0

c168

c168

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
552.0, 744.0

c169

c169

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
171.1739541254915, 508.0

c17

c17

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
474.4404476619766, 440.9393432241552

c170

c170

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
470.46988867442553, 699.7053735814004

c171

c171

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
168.97157769623155, 650.4759943306345

c172

c172

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
831.0, 472.0

c173

c173

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
841.7433776766208, 481.0

c174

c174

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
917.0, 472.0

c175

c175

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
916.0, 520.0

c176

c176

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
908.0, 529.0

c177

c177

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
914.5610156344095, 481.0

c178

c178

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
135.98658949977107, 476.0169871183663

c179

c179

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
164.0, 552.0

c18

c18

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
694.0, 204.0

c180

c180

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
964.0, 425.0

c181

c181

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
147.67963167245307, 525.1353182485898

c182

c182

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1055.0, 835.60738467846

c183

c183

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
993.0, 815.0

c184

c184

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
999.3328348449405, 821.0

c185

c185

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
943.8152001391701, 870.0

c186

c186

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
889.0, 818.5295573660936

c187

c187

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
912.5419624322474, 818.8499905641687

c188

c188

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
832.0, 883.9932582089723

c189

c189

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
341.0, 552.0

c19

c19

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
838.0, 897.4094520537384

c190

c190

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
987.0, 717.0

c191

c191

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
999.0, 760.0

c192

c192

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1133.0, 760.0

c193

c193

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
901.3297067625163, 775.0

c194

c194

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
928.0, 628.0

c195

c195

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
938.8063839788744, 637.0

c196

c196

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1001.0, 628.0

c197

c197

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
868.0, 812.8406661402685

c198

c198

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
827.0, 855.7854769022113

c199

c199

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
371.0, 93.0

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
333.0, 563.0

c20

c20

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
392.0, 1061.0

c200

c200

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
447.0, 1244.9382230137094

c201

c201

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
829.0, 803.2767863074105

c202

c202

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
529.0, 844.9307097006468

c203

c203

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
443.99311420452716, 628.0

c204

c204

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
863.6597214901759, 684.0

c205

c205

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
272.0, 552.0

c21

c21

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
333.0, 644.0

c22

c22

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
325.0, 653.0

c23

c23

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
337.0, 724.0

c24

c24

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
329.0, 734.0

c25

c25

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
270.0, 575.0

c26

c26

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
264.0, 575.0

c27

c27

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
172.82065424938904, 603.0

c28

c28

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
392.0, 600.0

c29

c29

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
351.0, 105.0

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
764.0, 928.0

c30

c30

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
295.0, 822.0

c31

c31

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
287.0, 829.0

c32

c32

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
299.9978375455748, 900.0

c33

c33

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
292.0, 907.0

c34

c34

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
189.0, 822.0

c35

c35

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
186.0, 901.0

c36

c36

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
120.0, 862.0

c37

c37

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
121.99966641647887, 936.0

c38

c38

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
362.0, 811.5298221281347

c39

c39

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
273.3000400080607, 120.93046609326488

c4

c4

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
366.36229006375015, 817.0

c40

c40

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
169.0, 770.0

c41

c41

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
572.0, 808.0

c42

c42

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
588.0, 883.2579303520877

c43

c43

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
649.9308381279196, 885.0496697522246

c44

c44

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
642.0, 889.0

c45

c45

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
718.0, 915.0

c46

c46

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
178.8653996385128, 687.0

c47

c47

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
178.8653996385128, 728.4613310803794

c48

c48

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
172.9891873950697, 633.0

c49

c49

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
252.0, 119.0

c5

c5

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
259.0, 1003.0

c50

c50

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
501.0, 1256.0

c51

c51

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
269.0, 1045.0

c52

c52

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
261.0, 1053.0

c53

c53

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
267.75042163582054, 1085.0

c54

c54

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
319.5066718613004, 1061.0

c55

c55

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
325.0, 1228.7074172808723

c56

c56

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
336.9977333899531, 1044.0

c57

c57

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
264.0, 1171.0

c58

c58

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
262.0, 1285.1716000756319

c59

c59

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
176.5357429061181, 217.0

c6

c6

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
507.9308417691747, 1200.0

c60

c60

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
262.0, 1260.8364087048146

c61

c61

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
456.0, 1184.0

c62

c62

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
464.0, 1095.8208100192876

c63

c63

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
529.0, 1076.0

c64

c64

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
529.0, 1089.0

c65

c65

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
703.0, 1110.0

c66

c66

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
568.0, 1122.0

c67

c67

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
652.0, 1087.0

c68

c68

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
556.0, 1136.0

c69

c69

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
170.0, 274.0

c7

c7

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
779.0, 1110.0

c70

c70

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
833.0, 1110.0

c71

c71

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
622.0, 1192.0

c72

c72

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
637.0, 1158.0

c73

c73

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
529.0, 1045.306715149602

c74

c74

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
529.0, 1072.0

c75

c75

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
703.0, 1042.0

c76

c76

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
704.0, 1074.0

c77

c77

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
755.0, 1042.0

c78

c78

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
810.0, 1053.4656813297545

c79

c79

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
269.0, 274.0

c8

c8

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
392.0, 552.0

c80

c80

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
398.5214432661302, 562.0

c81

c81

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
161.0, 436.0

c82

c82

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
79.88577539062544, 606.0

c83

c83

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
124.99718216142952, 993.0

c84

c84

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
67.0, 993.0

c85

c85

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
259.0, 994.0

c86

c86

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
516.0, 1016.0

c87

c87

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
332.8265514632087, 1061.0

c88

c88

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
340.0, 1235.246145839326

c89

c89

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
361.0, 274.0

c9

c9

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
328.0, 1320.0

c90

c90

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
668.0, 948.0

c91

c91

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
615.0, 967.9999209333727

c92

c92

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
506.0, 328.0

c93

c93

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
504.0, 341.4376015698018

c94

c94

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
575.0, 328.0

c95

c95

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
573.5538553641524, 341.5876987549066

c96

c96

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
554.0, 341.0

c97

c97

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
553.0, 284.0

c98

c98

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
350.71186709880146, 345.08675120494826

c99

c99

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back