1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/17905508.csml convertedTime:2009.07.02.15:36

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title A role for caspases in the differentiation of erythroid cells and macrophages.
Authors Droin N, Cathelin S, Jacquel A, Guery L, Garrido C, Fontenay M, Hermine O,Solary E.
Affiliation INSERM, UMR 866, F-21079 Dijon, France.
Abstract Several cysteine proteases of the caspase family play a central role in manyforms of cell death by apoptosis. Other enzymes of the family are involved incytokine maturation along inflammatory response. In recent years, severalcaspases involved in cell death were shown to play a role in other cellularprocesses such as proliferation and differentiation. In the present review, wesummarize the current knowledge of the role of caspases in the differentiationof erythroid cells and macrophages. Based on these two examples, we show thatthe nature of involved enzymes, the pathways leading to their activation inresponse to specific growth factors, and the specificity of the target proteinsthat are cleaved by the activated enzymes strongly differ from one cell type toanother. Deregulation of these pathways is thought to play a role in thepathophysiology of low-grade myelodysplastic syndromes, characterized byexcessive activation of caspases and erythroid precursor apoptosis, and that ofchronic myelomonocytic leukemia, characterized by a defective activation ofcaspases in monocytes exposed to M-CSF, which blocks their differentiation.
PMID 17905508
Model Abstract

Entity

MO000000011:ERK MO000000012:Grb-2 MO000000030:PI3K MO000000058:NF-kappaB MO000000065:RIP1 MO000000092:EpoR MO000000100:M-CSF MO000000146:Jak2 MO000004927:Fas MO000007995:M-CSF-1-R MO000016736:Ras MO000016777:Sos MO000016876:STAT5 MO000016899:FADD MO000016900:Caspase-8 MO000016909:Caspase-2 MO000016924:Caspase-3 MO000016936:MAP MO000016985:Cytochrome C MO000016986:Apaf-1 MO000016987:Caspase-9 MO000017066:Epo MO000017602:Caspase-6 MO000017603:Caspase-7 MO000017616:PAK2 MO000017669:proCaspase-8 MO000017670:proCaspase-2 MO000017671:proCaspase-3 MO000017811:proCaspase-9 MO000017945:FLIP-L MO000017946:FLIP-S MO000018906:proCaspase-7 MO000019238:alpha-tubulin MO000019718:Cdc42:GTP MO000020340:vinculin MO000021614:Hsp70 {nucleolus} MO000032136:proCaspase-6 MO000032476:GATA-1 MO000045126:nucleophosmin MO000097692:Acinus e1: e10: e11:2(small subunit of caspase-3) e12:2(small subunit of caspase-6) e13:2(large subunit of caspase-7) e14:death receptor ligand e15:death receptor ligand: Fas e16:2(small subunit of caspase-7) e17:death receptor ligand: Fas: FADD: proCaspase-8 e18:Apaf-1 oligomer e19:Apaf-1 olgomer: proCaspase-9 e2: e20:Epo: EpoR: Jak2 e21:Epo: EpoR dimer: Jak2 e22:EpoR: Jak2 e23:Epo: EpoR dimer {p}: Jak2 {p} e24:Epo: EpoR dimer: Jak2 {p} e25:Epo: EpoR dimer {p}: Jak2 {p}: STAT5 e26:Epo: EpoR dimer {p}: Jak2 {p}: STAT5 dimer e27:Epo: EpoR dimer {p}: Jak2 {p}: STAT5 dimer {p} e28:Epo: EpoR dimer {p}: Jak2 {p}: STAT5 dimer {p}: PI3K e29:Epo: EpoR dimer {p}: Jak2 {p}: Grb-2 e3: e30:Epo: EpoR dimer {p}: Jak2 {p}: Grb-2: Sos e31:MAP {activated} e32:Ras {activated} e33:GATA-1 {activated} e34:Bcl-Xl e35:Caspase-3 e36:Caspase-7 e37:Hsp70 {nucleolus}: GATA-1 e38:Hsp70 e39:M-CSF: M-CSF-1-R e4: e40:M-CSF: M-CSF-1-R [p} dimer: PI3K e41:M-CSF: M-CSF-1-R [p} e42:M-CSF: M-CSF-1-R [p} dimer e43:PARP1 e44:Lamin-B e45:PARP1 remnants e46:Acinus remnants e47:Lamin-B remnants e48:M-CSF: M-CSF-1-R [p} dimer: proCaspase-8 e49:M-CSF: M-CSF-1-R [p} dimer: Caspase-8: FADD: RIP1: FLIP-L: FLIP-S e5:2(large subunit of caspase-3) e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:2(large subunit of caspase-6) e60: e61: e62: e63:M-CSF: M-CSF-1-R [p} dimer: Caspase-8 e64:M-CSF: M-CSF-1-R [p} dimer: Caspase-8: FADD e65:RIP1 fragment e66:NF-kappaB {activated} e67:PAK2 {activated} e68:nucleophosmin {activated} e69:alpha-tubulin remnants e7: e70:vinculin remnants e71:PAI-2 remnants e72:PAI-2 e73:FLIP-L remnant e74:FLIP-S remnant e75:M-CSF: M-CSF-1-R [p} dimer e76:M-CSF: M-CSF-1-R [p} dimer: ERK e77:Rac: GTP e78:death receptor ligand: Fas: FADD 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 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 p6 p7 p8 p9
Model Detail
314.0, 862.0
35.0, 35.0

ERK

--

MO000000011

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p55

true true true true

csml-variable:Double

m80

10

false

infinite

0

unit false false false
TRANSPATHMO000000011

--

Go back
944.0, 1001.0
32.0, 32.0

Grb-2

--

MO000000012

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p23

true true true true

csml-variable:Double

m30

10

false

infinite

0

unit false false false
InterProIPR001452
TRANSPATHMO000000012

--

Go back
889.0, 846.0
30.0, 30.0

PI3K

--

MO000000030

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p22 p40

true true true true

csml-variable:Double

m28

10

false

infinite

0

unit false false false
TRANSPATHMO000000030

--

Go back
767.0, 1239.0
34.0, 34.0

NF-kappaB

--

MO000000058

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p48

true true true true

csml-variable:Double

m69

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
322.0, 1038.0
28.0, 28.0

RIP1

--

MO000000065

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p45

true true true true

csml-variable:Double

m64

10

false

infinite

0

unit false false false
InterProIPR000198
TRANSPATHMO000000065

--

Go back
1003.0, 144.0
33.0, 33.0

EpoR

--

MO000000092

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p16

true true true true

csml-variable:Double

m82

10

false

infinite

0

unit false false false
InterProIPR003528
TRANSPATHMO000000092

--

Go back
161.0, 537.0
30.0, 30.0

M-CSF

--

MO000000100

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p37

true true true true

csml-variable:Double

m89

10

false

infinite

0

unit false false false
InterProIPR008001
TRANSPATHMO000000100

--

Go back
953.0, 210.0
29.0, 29.0

Jak2

--

MO000000146

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p16

true true true true

csml-variable:Double

m130

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000000146

--

Go back
644.0, 156.0
39.0, 39.0

Fas

--

MO000004927

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p10

true true true true

csml-variable:Double

m580

10

false

infinite

0

unit false false false
InterProIPR001368
TRANSPATHMO000004927

--

Go back
235.0, 527.0
34.0, 34.0

M-CSF-1-R

--

MO000007995

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p37

true true true true

csml-variable:Double

m1031

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000007995

--

Go back
877.0, 1154.0
30.0, 30.0

Ras

--

MO000016736

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p25

true true true true

csml-variable:Double

m1688

10

false

infinite

0

unit false false false
TRANSPATHMO000016736

--

Go back
894.0, 1063.0
36.0, 36.0

Sos

--

MO000016777

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p24

true true true true

csml-variable:Double

m1720

10

false

infinite

0

unit false false false
TRANSPATHMO000016777

--

Go back
887.0, 608.0
33.5, 33.5

STAT5

--

MO000016876

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p19

true true true true

csml-variable:Double

m1798

10

false

infinite

0

unit false false false
TRANSPATHMO000016876

--

Go back
675.0, 220.0
34.0, 34.0

FADD

--

MO000016899

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p45 p58

true true true true

csml-variable:Double

m1814

10

false

infinite

0

unit false false false
InterProIPR001875
TRANSPATHMO000016899

--

Go back
891.0, 299.0
34.0, 34.0

Caspase-8

--

MO000016900

cso30:c:Protein

cso30:i:CC_CellComponent

--

p8

p27

true true true true

csml-variable:Double

m1815

10

false

infinite

0

unit false false false
TRANSPATHMO000016900

--

Go back
676.0, 341.0
32.0, 32.0

Caspase-2

--

MO000016909

cso30:c:Protein

cso30:i:CC_CellComponent

--

p7

--

true true true true

csml-variable:Double

m1824

10

false

infinite

0

unit false false false
TRANSPATHMO000016909

--

Go back
538.0, 564.0
34.0, 34.0

Caspase-3

--

MO000016924

cso30:c:Protein

cso30:i:CC_CellComponent

--

p4

p31 p41 p42 p43 p49 p50

true true true true

csml-variable:Double

m1839

10

false

infinite

0

unit false false false
TRANSPATHMO000016924

--

Go back
876.0, 1280.0
32.0, 32.0

MAP

--

MO000016936

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p26

true true true true

csml-variable:Double

m1849

10

false

infinite

0

unit false false false
TRANSPATHMO000016936

--

Go back
387.0, 232.0
34.0, 34.0

Cytochrome C

--

MO000016985

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p12

true true true true

csml-variable:Double

m1889

10

false

infinite

0

unit false false false
InterProIPR002327
TRANSPATHMO000016985

--

Go back
378.0, 283.0
28.0, 28.0

Apaf-1

--

MO000016986

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p12

true true true true

csml-variable:Double

m1890

10

false

infinite

0

unit false false false
InterProIPR000767
TRANSPATHMO000016986

--

Go back
449.0, 506.0
30.0, 30.0

Caspase-9

--

MO000016987

cso30:c:Protein

cso30:i:CC_CellComponent

--

p9 p30

--

true true true true

csml-variable:Double

m1891

10

false

infinite

0

unit false false false
TRANSPATHMO000016987

--

Go back
1089.0, 318.0
29.0, 29.0

Epo

--

MO000017066

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p14

true true true true

csml-variable:Double

m1958

10

false

infinite

0

unit false false false
InterProIPR003013
TRANSPATHMO000017066

--

Go back
295.0, 468.0
34.0, 34.0

Caspase-6

--

MO000017602

cso30:c:Protein

cso30:i:CC_CellComponent

--

p5

--

true true true true

csml-variable:Double

m2381

10

false

infinite

0

unit false false false
TRANSPATHMO000017602

--

Go back
607.0, 492.0
34.0, 34.0

Caspase-7

--

MO000017603

cso30:c:Protein

cso30:i:CC_CellComponent

--

p6

p32

true true true true

csml-variable:Double

m2382

10

false

infinite

0

unit false false false
TRANSPATHMO000017603

--

Go back
640.0, 568.0
32.0, 32.0

PAK2

--

MO000017616

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p49 p56 p57

true true true true

csml-variable:Double

m2394

10

false

infinite

0

unit false false false
TRANSPATHMO000017616

--

Go back
783.0, 263.0
34.0, 34.0

proCaspase-8

--

MO000017669

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p11 p44

true true true true

csml-variable:Double

m2432

10

false

infinite

0

unit false false false
InterProIPR001309
TRANSPATHMO000017669

--

Go back
671.0, 268.0
34.0, 34.0

proCaspase-2

--

MO000017670

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p7

true true true true

csml-variable:Double

m2433

10

false

infinite

0

unit false false false
InterProIPR001309
TRANSPATHMO000017670

--

Go back
533.0, 275.0
36.0, 36.0

proCaspase-3

--

MO000017671

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1

true true true true

csml-variable:Double

m2434

10

false

infinite

0

unit false false false
InterProIPR001309
TRANSPATHMO000017671

--

Go back
388.0, 449.0
31.0, 31.0

proCaspase-9

--

MO000017811

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p13 p9 p30

true true true true

csml-variable:Double

m2563

10

false

infinite

0

unit false false false
InterProIPR001309
TRANSPATHMO000017811

--

Go back
317.0, 1133.0
30.0, 30.0

FLIP-L

--

MO000017945

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p45

true true true true

csml-variable:Double

m2682

10

false

infinite

0

unit false false false
TRANSPATHMO000017945

--

Go back
336.0, 1088.0
32.0, 32.0

FLIP-S

--

MO000017946

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p45

true true true true

csml-variable:Double

m2683

10

false

infinite

0

unit false false false
TRANSPATHMO000017946

--

Go back
549.0, 222.0
38.0, 38.0

proCaspase-7

--

MO000018906

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p3

true true true true

csml-variable:Double

m3523

10

false

infinite

0

unit false false false
InterProIPR001309
TRANSPATHMO000018906

--

Go back
302.0, 1226.0
28.0, 28.0

alpha-tubulin

--

MO000019238

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p51

true true true true

csml-variable:Double

m3822

10

false

infinite

0

unit false false false
TRANSPATHMO000019238

--

Go back
704.0, 496.0
40.0, 40.0

Cdc42:GTP

--

MO000019718

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p56

true true true true

csml-variable:Double

m4251

10

false

infinite

0

unit false false false
TRANSPATHMO000019718

--

Go back
415.0, 1203.0
25.0, 25.0

vinculin

--

MO000020340

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p52

true true true true

csml-variable:Double

m4841

10

false

infinite

0

unit false false false
InterProIPR000633
TRANSPATHMO000020340

--

Go back
521.0, 1057.0
29.0, 29.0

Hsp70 {nucleolus}

--

MO000021614

cso30:c:Protein

cso30:i:CC_CellComponent

--

p36

p34 p35

true true true true

csml-variable:Double

m5956

10

false

infinite

0

unit false false false
InterProIPR001023
TRANSPATHMO000021614

--

Go back
315.0, 232.0
34.0, 34.0

proCaspase-6

--

MO000032136

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p2

true true true true

csml-variable:Double

m11106

10

false

infinite

0

unit false false false
InterProIPR001309
TRANSPATHMO000032136

--

Go back
628.0, 976.0
32.0, 32.0

GATA-1

--

MO000032476

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p27 p28 p34

true true true true

csml-variable:Double

m11427

10

false

infinite

0

unit false false false
InterProIPR000679
TRANSPATHMO000032476

--

Go back
643.0, 659.0
34.0, 34.0

nucleophosmin

--

MO000045126

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p50

true true true true

csml-variable:Double

m22786

10

false

infinite

0

unit false false false
TRANSPATHMO000045126

--

Go back
440.0, 637.0
32.0, 32.0

Acinus

--

MO000097692

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p42

true true true true

csml-variable:Double

m70781

10

false

infinite

0

unit false false false
TRANSPATHMO000097692

--

Go back
222.75, 139.9969080091176
856.2594311764528, 1243.2886940682085

--

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
231.0, 159.0
829.9775981223105, 1167.545103664102

--

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
561.5, 438.125
28.519999999999996, 21.389999999999993

2(small subunit of caspase-3)

--

e11

cso30:c:Protein

cso30:i:CC_Cytosol

--

p1

p4

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
325.5, 378.125
28.68000000000001, 21.51

2(small subunit of caspase-6)

--

e12

cso30:c:Protein

cso30:i:CC_Cytosol

--

p2

p5

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
600.5, 351.125
31.91084725296841, 19.67835580599718

2(large subunit of caspase-7)

--

e13

cso30:c:Protein

cso30:i:CC_Cytosol

--

p3

p6

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
710.5, 80.375
34.80667838312828, 22.624340949033396

death receptor ligand

--

e14

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p10

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
774.375, 144.5
28.136866915150186, 54.45845209383907

death receptor ligand: Fas

--

e15

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p10 p8

p58

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
642.5, 399.125
27.399999999999995, 20.549999999999997

2(small subunit of caspase-7)

--

e16

cso30:c:Protein

cso30:i:CC_Cytosol

--

p3

p6

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
928.5, 118.0
31.0, 60.0

death receptor ligand: Fas: FADD: proCaspase-8

--

e17

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p11

p8

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
378.5, 323.5
34.0, 34.0

Apaf-1 oligomer

--

e18

cso30:c:Complex

cso30:i:CC_Cytosol

--

p12

p13

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
441.625, 386.5
36.75, 45.0

Apaf-1 olgomer: proCaspase-9

--

e19

cso30:c:Complex

cso30:i:CC_Cytosol

--

p13

--

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
222.75, 139.9969080091176
856.2594311764528, 1243.2886940682085

--

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
1020.375, 378.5
26.52603595702697, 51.34071475553607

Epo: EpoR: Jak2

--

e20

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p14

p15 p36

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
1018.375, 449.5
27.973744792808596, 54.1427318570489

Epo: EpoR dimer: Jak2

--

e21

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p15

p1 p3 p17 p7 p30

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
1013.625, 250.5
36.75, 45.0

EpoR: Jak2

--

e22

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p16

p14

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
1017.375, 593.5
33.01693707520281, 63.90374917781188

Epo: EpoR dimer {p}: Jak2 {p}

--

e23

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p18

p19 p23

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
1016.375, 518.5
31.467276912957686, 60.9044069283052

Epo: EpoR dimer: Jak2 {p}

--

e24

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p17

p18

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
1012.375, 674.5
31.596415259811444, 61.15435211576409

Epo: EpoR dimer {p}: Jak2 {p}: STAT5

--

e25

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p19

p20

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
1010.375, 742.5
35.477362420521814, 68.66586274939708

Epo: EpoR dimer {p}: Jak2 {p}: STAT5 dimer

--

e26

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p20

p21

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
1012.375, 823.5
38.37957684718264, 74.28305196228898

Epo: EpoR dimer {p}: Jak2 {p}: STAT5 dimer {p}

--

e27

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p21

p22

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false false false

--

Go back
1005.375, 909.5
45.34625082218812, 87.7669370752028

Epo: EpoR dimer {p}: Jak2 {p}: STAT5 dimer {p}: PI3K

--

e28

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p22

--

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
1013.375, 1045.5
36.39492435869327, 70.44178908134182

Epo: EpoR dimer {p}: Jak2 {p}: Grb-2

--

e29

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p23

p24

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false false false

--

Go back
239.87518862352903, 157.12209663264667
822.0090539293948, 1209.0383168211513

--

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
1011.375, 1129.5
41.1934334575751, 79.72922604691954

Epo: EpoR dimer {p}: Jak2 {p}: Grb-2: Sos

--

e30

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p24

p25

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
940.0, 1265.0
32.0, 32.0

MAP {activated}

--

e31

cso30:c:Protein

cso30:i:CC_CellComponent

--

p26

--

true true true true

csml-variable:Double

m33

10

false

infinite

0

unit false false false
TRANSPATHMO000016936

--

Go back
877.0, 1214.0
30.0, 30.0

Ras {activated}

--

e32

cso30:c:Protein

cso30:i:CC_CellComponent

--

p25

p26

true true true true

csml-variable:Double

m34

10

false

infinite

0

unit false false false
TRANSPATHMO000016736

--

Go back
748.0, 936.0
32.0, 32.0

GATA-1 {activated}

--

e33

cso30:c:Protein

cso30:i:CC_CellComponent

--

p27 p28

p29

true true true true

csml-variable:Double

m35

10

false

infinite

0

unit false false false
InterProIPR000679
TRANSPATHMO000032476

--

Go back
693.5, 1060.0
45.0, 24.0

Bcl-Xl

--

e34

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p29

--

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false false false

--

Go back
539.0, 915.0
34.0, 34.0

Caspase-3

--

e35

cso30:c:Protein

cso30:i:CC_CellComponent

--

p31

p28

true true true true

csml-variable:Double

m37

10

false

infinite

0

unit false false false
TRANSPATHMO000016924

--

Go back
607.0, 883.0
34.0, 34.0

Caspase-7

--

e36

cso30:c:Protein

cso30:i:CC_CellComponent

--

p32

--

true true true true

csml-variable:Double

m38

10

false

infinite

0

unit false false false
TRANSPATHMO000017603

--

Go back
629.625, 1033.5
36.75, 45.0

Hsp70 {nucleolus}: GATA-1

--

e37

cso30:c:Complex

cso30:i:CC_Nucleoplasm

--

p34

--

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false false false

--

Go back
337.0, 965.0
29.0, 29.0

Hsp70

--

e38

cso30:c:Protein

cso30:i:CC_CellComponent

--

p35

p36

true true true true

csml-variable:Double

m40

10

false

infinite

0

unit false false false
InterProIPR001023
TRANSPATHMO000021614

--

Go back
240.375, 581.5
23.25, 45.0

M-CSF: M-CSF-1-R

--

e39

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p37

p38

true true true true

csml-variable:Double

m41

0

false

infinite

0

unit false false false

--

Go back
271.5567875770579, 187.09117672382234
758.6458560223374, 1149.1001566387988

--

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
237.375, 819.5
29.448640648980486, 56.99736899802675

M-CSF: M-CSF-1-R [p} dimer: PI3K

--

e40

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p40

--

true true true true

csml-variable:Double

m42

0

false

infinite

0

unit false false false

--

Go back
240.375, 636.5
24.06561061170796, 46.578601183950894

M-CSF: M-CSF-1-R [p}

--

e41

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p38

p39

true true true true

csml-variable:Double

m43

0

false

infinite

0

unit false false false

--

Go back
239.375, 691.5
25.751205875904407, 49.84104363078273

M-CSF: M-CSF-1-R [p} dimer

--

e42

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p39

p54

true true true true

csml-variable:Double

m44

0

false

infinite

0

unit false false false

--

Go back
441.0, 558.0
30.0, 30.0

PARP1

--

e43

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p41

true true true true

csml-variable:Double

m45

10

false

infinite

0

unit false false false
InterProIPR008288
TRANSPATHMO000018318

--

Go back
445.0, 698.0
30.0, 30.0

Lamin-B

--

e44

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p43

true true true true

csml-variable:Double

m46

10

false

infinite

0

unit false false false
Affymetrix100132_at
EnsemblENSMUSG00000024590
ProteomeHumanPSD/Lmnb1
RGDLmnb1
RefSeqNM_010721
TRANSPATHMO000085282
UnigeneMm.4105
UniProtP14733

--

Go back
404.5, 594.25
30.73233773693279, 29.707926479035038

PARP1 remnants

--

e45

cso30:c:EntityBiological

cso30:i:CC_Cytosol

--

p41

--

true true true true

csml-variable:Double

m47

0

false

infinite

0

unit false false false

--

Go back
408.5, 662.25
30.628948879954038, 29.60798391728892

Acinus remnants

--

e46

cso30:c:EntityBiological

cso30:i:CC_Cytosol

--

p42

--

true true true true

csml-variable:Double

m48

0

false

infinite

0

unit false false false

--

Go back
410.5, 724.25
26.596783457782884, 25.71022400919012

Lamin-B remnants

--

e47

cso30:c:EntityBiological

cso30:i:CC_Cytosol

--

p43

--

true true true true

csml-variable:Double

m49

0

false

infinite

0

unit false false false

--

Go back
239.375, 975.5
33.68981582986187, 65.20609515457137

M-CSF: M-CSF-1-R [p} dimer: proCaspase-8

--

e48

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p44

p46

true true true true

csml-variable:Double

m63

0

false

infinite

0

unit false false false

--

Go back
237.375, 1255.5
37.91060074545056, 73.37535628151721

M-CSF: M-CSF-1-R [p} dimer: Caspase-8: FADD: RIP1: FLIP-L: FLIP-S

--

e49

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p45

p47 p51 p52 p53

true true true true

csml-variable:Double

m65

0

false

infinite

0

unit false false false

--

Go back
519.5, 406.125
33.879050110686244, 20.892080901589857

2(large subunit of caspase-3)

--

e5

cso30:c:Protein

cso30:i:CC_Cytosol

--

p1

p4

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
415.0, 811.0
425.4694351312365, 385.85403148773247

--

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
460.9538682264648, 820.1441796027298
248.78473488120727, 373.969410394681

--

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
420.54615651009055, 816.1500024736553
414.37712211105554, 375.5540265404211

--

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
421.3384645829607, 816.9423105465255
412.7925059653152, 373.969410394681

--

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
415.0, 811.0
425.4694351312365, 385.85403148773247

--

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
415.0, 811.0
425.4694351312365, 385.85403148773247

--

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
421.3384645829607, 816.9423105465255
412.7925059653152, 373.969410394681

--

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
725.584764565074, 969.4616145740176
26.580992563455023, 24.06279326796983

--

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
655.8616541525063, 1080.3847447758294
75.2692669226582, 68.13849426682752

--

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
415.0, 811.0
425.4694351312365, 385.85403148773247

--

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
295.5, 347.125
32.3576172268062, 19.953863956530483

2(large subunit of caspase-6)

--

e6

cso30:c:Protein

cso30:i:CC_Cytosol

--

p2

p5

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
515.2807519087002, 982.4703432550382
13.473991848940734, 6.487477556897394

--

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
514.8308171816308, 963.1231499910567
46.11830952460786, 83.01295714429413

--

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
534.1780104456128, 1017.1153172393788
7.198955633109511, 7.198955633109514

--

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
239.375, 1051.5
33.14607542205657, 64.15369436527078

M-CSF: M-CSF-1-R [p} dimer: Caspase-8

--

e63

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p46

p1 p45

true true true true

csml-variable:Double

m66

0

false

infinite

0

unit false false false

--

Go back
558.375, 1316.5
36.184224950668714, 70.03398377548784

M-CSF: M-CSF-1-R [p} dimer: Caspase-8: FADD

--

e64

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p47

--

true true true true

csml-variable:Double

m67

0

false

infinite

0

unit false false false

--

Go back
692.5, 1297.25
30.663411832280296, 29.64129810453762

RIP1 fragment

--

e65

cso30:c:EntityBiological

cso30:i:CC_Cytosol

--

p47

p48

true true true true

csml-variable:Double

m68

0

false

infinite

0

unit false false false

--

Go back
819.0, 1223.0
34.0, 34.0

NF-kappaB {activated}

--

e66

cso30:c:Protein

cso30:i:CC_CellComponent

--

p48

--

true true true true

csml-variable:Double

m70

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
644.0, 616.0
32.0, 32.0

PAK2 {activated}

--

e67

cso30:c:Protein

cso30:i:CC_CellComponent

--

p49 p56 p57

--

true true true true

csml-variable:Double

m71

10

false

infinite

0

unit false false false
TRANSPATHMO000017616

--

Go back
587.0, 719.0
34.0, 34.0

nucleophosmin {activated}

--

e68

cso30:c:Protein

cso30:i:CC_CellComponent

--

p50

--

true true true true

csml-variable:Double

m72

10

false

infinite

0

unit false false false
TRANSPATHMO000045126

--

Go back
329.5, 1178.25
28.630097645031586, 27.675761056863873

alpha-tubulin remnants

--

e69

cso30:c:EntityBiological

cso30:i:CC_Cytosol

--

p51

--

true true true true

csml-variable:Double

m73

0

false

infinite

0

unit false false false

--

Go back
234.0, 145.0
839.7237354966342, 1189.8668429177399

--

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
437.5, 1170.25
28.630097645031586, 27.675761056863873

vinculin remnants

--

e70

cso30:c:EntityBiological

cso30:i:CC_Cytosol

--

p52

--

true true true true

csml-variable:Double

m74

0

false

infinite

0

unit false false false

--

Go back
554.5, 1267.25
26.56232050545663, 25.676909821941415

PAI-2 remnants

--

e71

cso30:c:EntityBiological

cso30:i:CC_Cytosol

--

p53

--

true true true true

csml-variable:Double

m75

0

false

infinite

0

unit false false false

--

Go back
481.0, 1217.0
29.0, 29.0

PAI-2

--

e72

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p53

true true true true

csml-variable:Double

m76

10

false

infinite

0

unit false false false
TRANSPATHMO000064072

--

Go back
598.5, 1239.25
26.45893164847789, 25.576967260195293

FLIP-L remnant

--

e73

cso30:c:EntityBiological

cso30:i:CC_Cytosol

--

p47

--

true true true true

csml-variable:Double

m77

0

false

infinite

0

unit false false false

--

Go back
685.5, 1242.25
28.785180930499713, 27.825674899483058

FLIP-S remnant

--

e74

cso30:c:EntityBiological

cso30:i:CC_Cytosol

--

p47

--

true true true true

csml-variable:Double

m78

0

false

infinite

0

unit false false false

--

Go back
240.5, 758.0
24.590659942994954, 47.59482569611927

M-CSF: M-CSF-1-R [p} dimer

--

e75

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p54

p40 p44 p55

true true true true

csml-variable:Double

m79

0

false

infinite

0

unit false false false

--

Go back
246.375, 908.5
28.22522473141855, 54.629467222100416

M-CSF: M-CSF-1-R [p} dimer: ERK

--

e76

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p55

--

true true true true

csml-variable:Double

m81

0

false

infinite

0

unit false false false

--

Go back
751.0, 615.0
34.0, 34.0

Rac: GTP

--

e77

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p57

true true true true

csml-variable:Double

m84

10

false

infinite

0

unit false false false
TRANSPATHMO000000057

--

Go back
859.25, 132.0
24.981473361105024, 48.35123876342908

death receptor ligand: Fas: FADD

--

e78

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p58

p11

true true true true

csml-variable:Double

m83

0

false

infinite

0

unit false false false

--

Go back
237.0, 166.0
805.5569854171277, 1169.6687428256696

--

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
245.0, 187.0
801.8791759029863, 1154.3288303559784

--

e9

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Cytoplasm

--

--

--

true true true true

csml-variable:Double

m9

0

false

infinite

0

unit false true false

--

Go back
536.0, 342.0
30.0, 30.0

p1

p1

cso30:i:ME_Cleavage

cso30:i:CC_Cytosol

--

MO000017671 e21 e63

e5 e11

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c1 : 1
stoichiometry:c22 : 1
stoichiometry:c138 : 1
stoichiometry:c4 : 1
stoichiometry:c5 : 1

m2434*m21*m66*0.1

nodelay

--

true

0

false

PMID: 17905508 those with a short prodomain (procaspase-3, -6 and -7) exist in the cells as dimers that require proteolysis at internal aspartate residues to generate two large and two small subunits whose heterodimerization forms the active enzyme. PMID: 17905508, 14976035, 12438425, 11208865 Caspase-3, together with caspase-9, -7 and -2, are transiently activated during erythroid differentiation induced by Epo and caspase inhibition completely inhibits erythroid differentiation at the basophilic erythroblast stage.

Go back
713.0, 161.0
30.0, 30.0

p10

p10

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

e14 MO000004927

e15

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c25 : 1
stoichiometry:c26 : 1
stoichiometry:c28 : 1

m14*m580*0.1

nodelay

--

true

0

false

PMID: 17905508 Interaction of a death receptor such as Fas (CD95), with its ligand, triggers formation of a death-inducing signaling complex (DISC), including the adaptor molecule FADD, which in turn recruits procaspase-8.

Go back
841.0, 237.0
30.0, 30.0

p11

p11

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

MO000017669 e78

e17

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c20 : 1
stoichiometry:c30 : 1
stoichiometry:c29 : 1

m2432*m83*0.1

nodelay

--

true

0

false

PMID: 17905508 Interaction of a death receptor such as Fas (CD95), with its ligand, triggers formation of a death-inducing signaling complex (DISC), including the adaptor molecule FADD, which in turn recruits procaspase-8.

Go back
445.0, 234.0
30.0, 30.0

p12

p12

cso30:i:ME_Polymerization

cso30:i:CC_Cytosol

--

MO000016985 MO000016986

e18

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c21 : 1
stoichiometry:c32 : 1
stoichiometry:c33 : 1

m1889*m1890*0.1

nodelay

--

true

0

false

PMID: 17905508 One of the soluble molecules subsequently released in the cytosol is cytochrome c, which induces Apaf-1 (apoptotic protease-activating factor 1) oligomerization and procaspase-9 recruitment and activation in the so-called apoptosome.

Go back
445.0, 326.0
30.0, 30.0

p13

p13

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000017811 e18

e19

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c35 : 1
stoichiometry:c34 : 1
stoichiometry:c36 : 1

m2563*m18*0.1

nodelay

--

true

0

false

PMID: 17905508 One of the soluble molecules subsequently released in the cytosol is cytochrome c, which induces Apaf-1 (apoptotic protease-activating factor 1) oligomerization and procaspase-9 recruitment and activation in the so-called apoptosome.

Go back
1017.0, 318.0
30.0, 30.0

p14

p14

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_ExternalSideOfPlasmaMembrane_

--

MO000017066 e22

e20

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c39 : 1
stoichiometry:c45 : 1
stoichiometry:c40 : 1

m1958*m22*0.1

nodelay

--

true

0

false

PMID: 17905508, 8343951 The binding of one Epo molecule to its receptor, which exists as a preformed dimer or dimerizes upon Epo binding, induces a conformational change that activated the constitutively associated JAK2 (Janus family tyrosine protein kinase 2) by transphosphorylation.

Go back
949.0, 390.0
30.0, 30.0

p15

p15

cso30:i:ME_Dimerization

cso30:i:CC_Cytosol

--

e20

e21

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c41 : 1
stoichiometry:c42 : 1

m20*0.1

nodelay

--

true

0

false

PMID: 17905508, 8343951 The binding of one Epo molecule to its receptor, which exists as a preformed dimer or dimerizes upon Epo binding, induces a conformational change that activated the constitutively associated JAK2 (Janus family tyrosine protein kinase 2) by transphosphorylation.

Go back
1005.0, 202.0
30.0, 30.0

p16

p16

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

MO000000146 MO000000092

e22

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c38 : 1
stoichiometry:c43 : 1
stoichiometry:c44 : 1

m130*m82*0.1

nodelay

--

true

0

false

PMID: 17905508, 8343951 The binding of one Epo molecule to its receptor, which exists as a preformed dimer or dimerizes upon Epo binding, induces a conformational change that activated the constitutively associated JAK2 (Janus family tyrosine protein kinase 2) by transphosphorylation.

Go back
949.0, 477.0
30.0, 30.0

p17

p17

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e21

e24

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c46 : 1
stoichiometry:c47 : 1

m21*0.1

nodelay

--

true

0

false

PMID: 17905508, 8343951 The binding of one Epo molecule to its receptor, which exists as a preformed dimer or dimerizes upon Epo binding, induces a conformational change that activated the constitutively associated JAK2 (Janus family tyrosine protein kinase 2) by transphosphorylation.

Go back
949.0, 534.0
30.0, 30.0

p18

p18

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e24

e23

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c49 : 1
stoichiometry:c50 : 1

m24*0.1

nodelay

--

true

0

false

PMID: 17905508 In turn, JAK2 molecules phosphorylate the eight tyrosine residues in the cytoplasmic domain of the Epo receptor, which then serve as docking sites for signaling molecules that contain Src homology 2 (SH2) domains such as STAT5 (Signal Transducer and Activator of Transcription 5), leading to its homodimerization and activation through phosphorylation.

Go back
949.0, 610.0
30.0, 30.0

p19

p19

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000016876 e23

e25

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c51 : 1
stoichiometry:c52 : 1
stoichiometry:c53 : 1

m1798*m23*0.1

nodelay

--

true

0

false

PMID: 17905508 In turn, JAK2 molecules phosphorylate the eight tyrosine residues in the cytoplasmic domain of the Epo receptor, which then serve as docking sites for signaling molecules that contain Src homology 2 (SH2) domains such as STAT5 (Signal Transducer and Activator of Transcription 5), leading to its homodimerization and activation through phosphorylation.

Go back
317.0, 286.0
30.0, 30.0

p2

p2

cso30:i:ME_Cleavage

cso30:i:CC_Cytosol

--

MO000032136

e6 e12

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c2 : 1
stoichiometry:c6 : 1
stoichiometry:c7 : 1

m11106*0.1

nodelay

--

true

0

false

PMID: 17905508 those with a short prodomain (procaspase-3, -6 and -7) exist in the cells as dimers that require proteolysis at internal aspartate residues to generate two large and two small subunits whose heterodimerization forms the active enzyme.

Go back
937.0, 690.0
30.0, 30.0

p20

p20

cso30:i:ME_Dimerization

cso30:i:CC_Cytosol

--

e25

e26

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c54 : 1
stoichiometry:c55 : 1

m25*0.1

nodelay

--

true

0

false

PMID: 17905508 In turn, JAK2 molecules phosphorylate the eight tyrosine residues in the cytoplasmic domain of the Epo receptor, which then serve as docking sites for signaling molecules that contain Src homology 2 (SH2) domains such as STAT5 (Signal Transducer and Activator of Transcription 5), leading to its homodimerization and activation through phosphorylation.

Go back
937.0, 762.0
30.0, 30.0

p21

p21

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e26

e27

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c56 : 1
stoichiometry:c57 : 1

m26*0.1

nodelay

--

true

0

false

PMID: 17905508 In turn, JAK2 molecules phosphorylate the eight tyrosine residues in the cytoplasmic domain of the Epo receptor, which then serve as docking sites for signaling molecules that contain Src homology 2 (SH2) domains such as STAT5 (Signal Transducer and Activator of Transcription 5), leading to its homodimerization and activation through phosphorylation.

Go back
945.0, 846.0
30.0, 30.0

p22

p22

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e27 MO000000030

e28

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c58 : 1
stoichiometry:c59 : 1
stoichiometry:c60 : 1

m27*m28*0.1

nodelay

--

true

0

false

PMID: 17905508 Other active signaling molecules recruited by the phosphorylated Epo receptor include the phopshatidylinositol- 3 kinase that, together with STAT5, promote erythroid cell survival, and son of sevenless protein recruited through the adaptor protein Grb-2 to activate the RAS/MAP (mitogen- activated protein) kinase pathway, thereby promoting proliferation.

Go back
1073.0, 1002.0
30.0, 30.0

p23

p23

cso30:i:ME_Binding

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

e23 MO000000012

e29

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c61 : 1
stoichiometry:c62 : 1
stoichiometry:c63 : 1

m23*m30*0.1

nodelay

--

true

0

false

PMID: 17905508 Other active signaling molecules recruited by the phosphorylated Epo receptor include the phopshatidylinositol- 3 kinase that, together with STAT5, promote erythroid cell survival, and son of sevenless protein recruited through the adaptor protein Grb-2 to activate the RAS/MAP (mitogen- activated protein) kinase pathway, thereby promoting proliferation.

Go back
953.0, 1066.0
30.0, 30.0

p24

p24

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000016777 e29

e30

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c64 : 1
stoichiometry:c65 : 1
stoichiometry:c66 : 1

m1720*m31*0.1

nodelay

--

true

0

false

PMID: 17905508 Other active signaling molecules recruited by the phosphorylated Epo receptor include the phopshatidylinositol- 3 kinase that, together with STAT5, promote erythroid cell survival, and son of sevenless protein recruited through the adaptor protein Grb-2 to activate the RAS/MAP (mitogen- activated protein) kinase pathway, thereby promoting proliferation.

Go back
933.0, 1154.0
30.0, 30.0

p25

p25

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e30 MO000016736

e32

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c67 : 1
stoichiometry:c70 : 1
stoichiometry:c71 : 1

m32*m1688*0.1

nodelay

--

true

0

false

PMID: 17905508 Other active signaling molecules recruited by the phosphorylated Epo receptor include the phopshatidylinositol- 3 kinase that, together with STAT5, promote erythroid cell survival, and son of sevenless protein recruited through the adaptor protein Grb-2 to activate the RAS/MAP (mitogen- activated protein) kinase pathway, thereby promoting proliferation.

Go back
941.0, 1214.0
30.0, 30.0

p26

p26

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000016936 e32

e31

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c68 : 1
stoichiometry:c72 : 1
stoichiometry:c69 : 1

m1849*m34*0.1

nodelay

--

true

0

false

PMID: 17905508 Other active signaling molecules recruited by the phosphorylated Epo receptor include the phopshatidylinositol- 3 kinase that, together with STAT5, promote erythroid cell survival, and son of sevenless protein recruited through the adaptor protein Grb-2 to activate the RAS/MAP (mitogen- activated protein) kinase pathway, thereby promoting proliferation.

Go back
689.0, 885.0
30.0, 30.0

p27

p27

cso30:i:ME_Cleavage

cso30:i:CC_Nucleoplasm

--

MO000032476 MO000016900

e33

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c76 : 1
stoichiometry:c73 : 1
stoichiometry:c78 : 1

m11427*m1815*0.1

nodelay

--

true

0

false

PMID: 17905508, 10359572, 10428030 In Epo-deprived as well as Fas-ligand treated immature erythroblasts, activated caspases cleave the transcription factor GATA-1. This transcription factor mediates Epo-induced up-regulation of the anti-apoptotic protein Bcl-XL.

Go back
697.0, 977.0
30.0, 30.0

p28

p28

cso30:i:ME_Cleavage

cso30:i:CC_Nucleoplasm

--

MO000032476 e35

e33

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c75 : 1
stoichiometry:c90 : 1
stoichiometry:c77 : 1

m11427*m37*0.1

nodelay

--

true

0

false

PMID: 17905508, 10359572, 10428030 In Epo-deprived as well as Fas-ligand treated immature erythroblasts, activated caspases cleave the transcription factor GATA-1. This transcription factor mediates Epo-induced up-regulation of the anti-apoptotic protein Bcl-XL. PMID: 17905508, 14976035, 12438425, 11208865 Caspase-3, together with caspase-9, -7 and -2, are transiently activated during erythroid differentiation induced by Epo and caspase inhibition completely inhibits erythroid differentiation at the basophilic erythroblast stage.

Go back
749.0, 1001.0
30.0, 30.0

p29

p29

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e33

e34

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c74 : 1
stoichiometry:c79 : 1

m35*0.1

nodelay

--

true

0

false

PMID: 17905508, 10359572, 10428030 In Epo-deprived as well as Fas-ligand treated immature erythroblasts, activated caspases cleave the transcription factor GATA-1. This transcription factor mediates Epo-induced up-regulation of the anti-apoptotic protein Bcl-XL.

Go back
593.0, 274.0
30.0, 30.0

p3

p3

cso30:i:ME_Cleavage

cso30:i:CC_Cytosol

--

MO000018906 e21

e13 e16

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c3 : 1
stoichiometry:c19 : 1
stoichiometry:c8 : 1
stoichiometry:c9 : 1

m3523*m21*0.1

nodelay

--

true

0

false

PMID: 17905508 those with a short prodomain (procaspase-3, -6 and -7) exist in the cells as dimers that require proteolysis at internal aspartate residues to generate two large and two small subunits whose heterodimerization forms the active enzyme. PMID: 17905508, 14976035, 12438425, 11208865 Caspase-3, together with caspase-9, -7 and -2, are transiently activated during erythroid differentiation induced by Epo and caspase inhibition completely inhibits erythroid differentiation at the basophilic erythroblast stage.

Go back
449.0, 450.0
30.0, 30.0

p30

p30

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000017811 e21

MO000016987

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c83 : 1
stoichiometry:c85 : 1
stoichiometry:c84 : 1

m2563*m21*0.1

nodelay

--

true

0

false

PMID: 17905508, 14976035, 12438425, 11208865 Caspase-3, together with caspase-9, -7 and -2, are transiently activated during erythroid differentiation induced by Epo and caspase inhibition completely inhibits erythroid differentiation at the basophilic erythroblast stage.

Go back
541.0, 825.0
30.0, 30.0

p31

p31

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

MO000016924

e35

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c86 : 1
stoichiometry:c88 : 1

m1839*0.1

nodelay

--

true

0

false

PMID: 17905508 Along erythroid differentiation, activated caspase-3 and, to a lower extent, caspase-7, are found in the nucleus where they co-localize with GATA-1 but this transcription factor is protected from caspase-mediated proteolysis through interaction with the chaperone heat shock protein Hsp70.

Go back
609.0, 825.0
30.0, 30.0

p32

p32

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

MO000017603

e36

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c87 : 1
stoichiometry:c89 : 1

m2382*0.1

nodelay

--

true

0

false

PMID: 17905508 Along erythroid differentiation, activated caspase-3 and, to a lower extent, caspase-7, are found in the nucleus where they co-localize with GATA-1 but this transcription factor is protected from caspase-mediated proteolysis through interaction with the chaperone heat shock protein Hsp70.

Go back
521.0, 977.0
30.0, 30.0

p34

p34

cso30:i:ME_Binding

cso30:i:CC_Nucleoplasm

--

MO000032476 MO000021614

e37

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c94 : 1
stoichiometry:c95 : 1
stoichiometry:c96 : 1

m11427*m5956*0.1

nodelay

--

true

0

false

PMID: 17905508 Along erythroid differentiation, activated caspase-3 and, to a lower extent, caspase-7, are found in the nucleus where they co-localize with GATA-1 but this transcription factor is protected from caspase-mediated proteolysis through interaction with the chaperone heat shock protein Hsp70.

Go back
421.0, 965.0
30.0, 30.0

p35

p35

cso30:i:ME_Translocation

cso30:i:CC_Nucleoplasm

--

MO000021614

e38

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c98 : 1
stoichiometry:c99 : 1

m5956*0.1

nodelay

--

true

0

false

PMID: 17905508 Epo starvation induces Hsp70 nucleus export and exposes GATA-1 to caspase-mediated cleavage.

Go back
441.0, 897.0
30.0, 30.0

p36

p36

cso30:i:ME_Translocation

cso30:i:CC_Nucleoplasm

--

e38 e20

MO000021614

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c97 : 1
stoichiometry:c101 : 1
stoichiometry:c100 : 1

m40*m20*0.1

nodelay

--

true

0

false

PMID: 17905508 In the presence of Epo, Hsp70 migrates in the nucleus when caspases are activated and protect GATA-1 from caspase-mediated cleavage.

Go back
161.0, 589.0
30.0, 30.0

p37

p37

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000000100 MO000007995

e39

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c102 : 1
stoichiometry:c103 : 1
stoichiometry:c104 : 1

m89*m1031*0.1

nodelay

--

true

0

false

PMID: 17905508 The growth factor M-CSF/CSF-1 is a disulfide-linked homodimer that binds to CSF-1 receptor, stabilizes its non-covalent dimerization, activates its kinase activity and stimulates its tyrosine phosphorylation.

Go back
297.0, 589.0
30.0, 30.0

p38

p38

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e39

e41

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c105 : 1
stoichiometry:c106 : 1

m41*0.1

nodelay

--

true

0

false

PMID: 17905508 The growth factor M-CSF/CSF-1 is a disulfide-linked homodimer that binds to CSF-1 receptor, stabilizes its non-covalent dimerization, activates its kinase activity and stimulates its tyrosine phosphorylation.

Go back
297.0, 645.0
30.0, 30.0

p39

p39

cso30:i:ME_Dimerization

cso30:i:CC_Cytosol

--

e41

e42

true true true true

--

and

mass

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

m43*0.1

nodelay

--

true

0

false

PMID: 17905508, 12966146 This limited phosphorylation induces the covalent dimerization of the receptor through disulfide binding, which activates a second wave of tyrosine phosphorylation of the receptor and its interaction with downstream signaling molecules that include phosphatidylinositol- 3-kinases, extracellular-signal-related kinases and Src kinases.

Go back
541.0, 498.0
30.0, 30.0

p4

p4

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e5 e11

MO000016924

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c11 : 1
stoichiometry:c16 : 1

m5*m11*0.1

nodelay

--

true

0

false

PMID: 17905508 those with a short prodomain (procaspase-3, -6 and -7) exist in the cells as dimers that require proteolysis at internal aspartate residues to generate two large and two small subunits whose heterodimerization forms the active enzyme.

Go back
297.0, 785.0
30.0, 30.0

p40

p40

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000000030 e75

e40

true true true true

--

and

mass

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

m28*m79*0.1

nodelay

--

true

0

false

PMID: 17905508, 12966146 This limited phosphorylation induces the covalent dimerization of the receptor through disulfide binding, which activates a second wave of tyrosine phosphorylation of the receptor and its interaction with downstream signaling molecules that include phosphatidylinositol- 3-kinases, extracellular-signal-related kinases and Src kinases.

Go back
489.0, 594.0
30.0, 30.0

p41

p41

cso30:i:ME_Cleavage

cso30:i:CC_Cytosol

--

MO000016924 e43

e45

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c112 : 1
stoichiometry:c115 : 1
stoichiometry:c116 : 1

m1839*m45*0.1

nodelay

--

true

0

false

PMID: 17905508 Activation of specific caspases in response to Epo in erythroid precursors leads to the specific cleavage of cellular targets such as PARP1, Acinus and Lamin B whereas the key differentiation- involved transcription factor GATA-1 is protected from cleavage by HSP70.

Go back
493.0, 662.0
30.0, 30.0

p42

p42

cso30:i:ME_Cleavage

cso30:i:CC_Cytosol

--

MO000016924 MO000097692

e46

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c113 : 1
stoichiometry:c117 : 1
stoichiometry:c118 : 1

m1839*m70781*0.1

nodelay

--

true

0

false

PMID: 17905508 Activation of specific caspases in response to Epo in erythroid precursors leads to the specific cleavage of cellular targets such as PARP1, Acinus and Lamin B whereas the key differentiation- involved transcription factor GATA-1 is protected from cleavage by HSP70.

Go back
497.0, 722.0
30.0, 30.0

p43

p43

cso30:i:ME_Cleavage

cso30:i:CC_Cytosol

--

MO000016924 e44

e47

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c114 : 1
stoichiometry:c119 : 1
stoichiometry:c120 : 1

m1839*m46*0.1

nodelay

--

true

0

false

PMID: 17905508 Activation of specific caspases in response to Epo in erythroid precursors leads to the specific cleavage of cellular targets such as PARP1, Acinus and Lamin B whereas the key differentiation- involved transcription factor GATA-1 is protected from cleavage by HSP70.

Go back
177.0, 797.0
30.0, 30.0

p44

p44

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000017669 e75

e48

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c122 : 1
stoichiometry:c121 : 1
stoichiometry:c123 : 1

m2432*m79*0.1

nodelay

--

true

0

false

PMID: 17905508, 17047155 In response to M-CSF/CSF-1, procaspase-8 interacts with the adaptor molecule FADD (Fas- Associated Death Domain), the serine threonine kinase RIP1 and the long and short isoforms of FLIP.

Go back
165.0, 1189.0
30.0, 30.0

p45

p45

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

MO000016899 MO000000065 MO000017945 MO000017946 e63

e49

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c124 : 1
stoichiometry:c126 : 1
stoichiometry:c127 : 1
stoichiometry:c128 : 1
stoichiometry:c131 : 1
stoichiometry:c129 : 1

m1814*m64*m2682*m2683*m66*0.1

nodelay

--

true

0

false

PMID: 17905508, 17047155 In response to M-CSF/CSF-1, procaspase-8 interacts with the adaptor molecule FADD (Fas- Associated Death Domain), the serine threonine kinase RIP1 and the long and short isoforms of FLIP.

Go back
173.0, 1069.0
30.0, 30.0

p46

p46

cso30:i:ME_UnknownActivation

cso30:i:CC_Extracellular

--

e48

e63

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c125 : 1
stoichiometry:c130 : 1

m63*0.1

nodelay

--

true

0

false

PMID: 17905508 Caspase-8 is activated in response to M-CSF that induces the formation of a multimolecular platform in which FADD, RIP1 and FLIP were identified.

Go back
637.0, 1297.0
30.0, 30.0

p47

p47

cso30:i:ME_Cleavage

cso30:i:CC_Cytosol

--

e49

e64 e65 e73 e74

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c132 : 1
stoichiometry:c133 : 1
stoichiometry:c134 : 1
stoichiometry:c154 : 1
stoichiometry:c155 : 1

m65*0.1

nodelay

--

true

0

false

PMID: 17905508 Interestingly, RIP1 is cleaved by caspase-8 in the multimolecular platform. PMID: 17905508, 17047155, 12393560 We also observed that another well identified caspase target, Lamin B, remained uncleaved whereas three other caspase targets, namely RIP1, FLIP and Acinus, were cleaved.

Go back
769.0, 1297.0
30.0, 30.0

p48

p48

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000000058 e65

e66

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c135 : 1
stoichiometry:c137 : 1
stoichiometry:c136 : 1

m69*0.1

nodelay

--

true

0

false

PMID: 17905508 The RIP1 cleavage generates a fragment that prevents the sustained activation of NF-kappaB, which is observed in monocytes undergoing differentiation into dendritic cells, and contributes to the down-regulation of NF-kappaB that characterizes the differentiation of monocytes into macrophage.

Go back
593.0, 573.0
30.0, 30.0

p49

p49

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000017616 MO000016924

e67

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c139 : 1
stoichiometry:c141 : 1
stoichiometry:c140 : 1

m2394*m1839*0.1

nodelay

--

true

0

false

PMID: 17905508 A cleavage fragment of RIP1, generated by active caspase-8, contributes to the down-regulation of NF-kappaB whereas caspase-3, activated downstream of caspase-8, cleaves other target proteins such as PAK2 and nucleophosmin that contribute to the differentiation.

Go back
297.0, 414.0
30.0, 30.0

p5

p5

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e6 e12

MO000017602

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c12 : 1
stoichiometry:c13 : 1
stoichiometry:c17 : 1

m6*m12*0.1

nodelay

--

true

0

false

PMID: 17905508 those with a short prodomain (procaspase-3, -6 and -7) exist in the cells as dimers that require proteolysis at internal aspartate residues to generate two large and two small subunits whose heterodimerization forms the active enzyme.

Go back
589.0, 661.0
30.0, 30.0

p50

p50

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000045126 MO000016924

e68

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c142 : 1
stoichiometry:c144 : 1
stoichiometry:c143 : 1

m22786*m1839*0.1

nodelay

--

true

0

false

PMID: 17905508 A cleavage fragment of RIP1, generated by active caspase-8, contributes to the down-regulation of NF-kappaB whereas caspase-3, activated downstream of caspase-8, cleaves other target proteins such as PAK2 and nucleophosmin that contribute to the differentiation.

Go back
369.0, 1225.0
30.0, 30.0

p51

p51

cso30:i:ME_Cleavage

cso30:i:CC_Cytosol

--

e49 MO000019238

e69

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c145 : 1
stoichiometry:c148 : 1
stoichiometry:c149 : 1

m65*m3822*0.1

nodelay

--

true

0

false

PMID: 17905508, 16636047 This approach, performed in the U937 cell line model, identified several proteins whose caspase-mediated cleavage was confirmed in primary monocytes exposed to M-CSF. These target proteins include p21-activated kinase-2, Nucleophosmin, a-Tubulin, Vinculin, Plasminogen Activator Inhibitory-2 (PAI-2), and several proteins of the hnRNP family.

Go back
429.0, 1245.0
30.0, 30.0

p52

p52

cso30:i:ME_Cleavage

cso30:i:CC_Cytosol

--

e49 MO000020340

e70

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c146 : 1
stoichiometry:c152 : 1
stoichiometry:c150 : 1

m65*m4841*0.1

nodelay

--

true

0

false

PMID: 17905508, 16636047 This approach, performed in the U937 cell line model, identified several proteins whose caspase-mediated cleavage was confirmed in primary monocytes exposed to M-CSF. These target proteins include p21-activated kinase-2, Nucleophosmin, a-Tubulin, Vinculin, Plasminogen Activator Inhibitory-2 (PAI-2), and several proteins of the hnRNP family.

Go back
481.0, 1269.0
30.0, 30.0

p53

p53

cso30:i:ME_Cleavage

cso30:i:CC_Cytosol

--

e49 e72

e71

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c147 : 1
stoichiometry:c153 : 1
stoichiometry:c151 : 1

m65*m76*0.1

nodelay

--

true

0

false

PMID: 17905508, 16636047 This approach, performed in the U937 cell line model, identified several proteins whose caspase-mediated cleavage was confirmed in primary monocytes exposed to M-CSF. These target proteins include p21-activated kinase-2, Nucleophosmin, a-Tubulin, Vinculin, Plasminogen Activator Inhibitory-2 (PAI-2), and several proteins of the hnRNP family.

Go back
297.0, 725.0
30.0, 30.0

p54

p54

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e42

e75

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c156 : 1
stoichiometry:c157 : 1

m44*0.1

nodelay

--

true

0

false

PMID: 17905508, 12966146 This limited phosphorylation induces the covalent dimerization of the receptor through disulfide binding, which activates a second wave of tyrosine phosphorylation of the receptor and its interaction with downstream signaling molecules that include phosphatidylinositol- 3-kinases, extracellular-signal-related kinases and Src kinases.

Go back
161.0, 861.0
30.0, 30.0

p55

p55

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000000011 e75

e76

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c158 : 1
stoichiometry:c159 : 1
stoichiometry:c160 : 1

m80*m79*0.1

nodelay

--

true

0

false

PMID: 17905508, 12966146 This limited phosphorylation induces the covalent dimerization of the receptor through disulfide binding, which activates a second wave of tyrosine phosphorylation of the receptor and its interaction with downstream signaling molecules that include phosphatidylinositol- 3-kinases, extracellular-signal-related kinases and Src kinases.

Go back
713.0, 569.0
30.0, 30.0

p56

p56

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000017616 MO000019718

e67

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c161 : 1
stoichiometry:c165 : 1
stoichiometry:c162 : 1

m2394*m4251*0.1

nodelay

--

true

0

false

PMID: 17905508 PAK-2 can be activated by the monomeric G proteins Cdc42 and Rac that, in their GTP-bound state, bind to a conserved region within the Nterminal domain of PAKs to release inhibition of the catalytic site by an overlapping autoinhibitory domain.

Go back
701.0, 617.0
30.0, 30.0

p57

p57

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000017616 e77

e67

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c163 : 1
stoichiometry:c166 : 1
stoichiometry:c164 : 1

m2394*m84*0.1

nodelay

--

true

0

false

PMID: 17905508 PAK-2 can be activated by the monomeric G proteins Cdc42 and Rac that, in their GTP-bound state, bind to a conserved region within the Nterminal domain of PAKs to release inhibition of the catalytic site by an overlapping autoinhibitory domain.

Go back
778.5, 222.5
27.0, 27.0

p58

p58

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e15 MO000016899

e78

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c27 : 1
stoichiometry:c167 : 1
stoichiometry:c168 : 1

m15*m1814*0.1

nodelay

--

true

0

false

PMID: 17905508 Interaction of a death receptor such as Fas (CD95), with its ligand, triggers formation of a death-inducing signaling complex (DISC), including the adaptor molecule FADD, which in turn recruits procaspase-8.

Go back
605.0, 434.0
30.0, 30.0

p6

p6

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e13 e16

MO000017603

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c14 : 1
stoichiometry:c15 : 1
stoichiometry:c18 : 1

m13*m16*0.1

nodelay

--

true

0

false

PMID: 17905508 those with a short prodomain (procaspase-3, -6 and -7) exist in the cells as dimers that require proteolysis at internal aspartate residues to generate two large and two small subunits whose heterodimerization forms the active enzyme.

Go back
721.0, 302.0
30.0, 30.0

p7

p7

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000017670 e21

MO000016909

true true true true

--

and

mass

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

m2433*m21*0.1

nodelay

--

true

0

false

PMID: 17905508, 14976035, 12438425, 11208865 Caspase-3, together with caspase-9, -7 and -2, are transiently activated during erythroid differentiation induced by Epo and caspase inhibition completely inhibits erythroid differentiation at the basophilic erythroblast stage.

Go back
893.0, 229.0
30.0, 30.0

p8

p8

cso30:i:ME_Dimerization

cso30:i:CC_Cytosol

--

e17

MO000016900 e15

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c23 : 1
stoichiometry:c31 : 1
stoichiometry:c48 : 1

m17*0.1

nodelay

--

true

0

false

PMID: 17905508 Procaspase-8 is then activated by proximity-induced dimerization within this oligomeric recruitment complex, which in turn activates the caspase cascade.

Go back
389.0, 506.0
30.0, 30.0

p9

p9

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000017811

MO000016987

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c24 : 1
stoichiometry:c37 : 1

m2563*0.1

nodelay

--

true

0

false

PMID: 17905508 One of the soluble molecules subsequently released in the cytosol is cytochrome c, which induces Apaf-1 (apoptotic protease-activating factor 1) oligomerization and procaspase-9 recruitment and activation in the so-called apoptosome.

Go back
551.0, 311.0

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
538.0, 427.0

c10

c10

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
463.0, 927.0

c100

c100

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
478.2345051843143, 419.0

c101

c101

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
176.0, 567.0

c102

c102

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
197.2608084334052, 557.0

c103

c103

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
191.0, 604.0

c104

c104

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
264.0, 604.0

c105

c105

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
269.91952058716754, 618.0

c106

c106

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
264.0, 660.0

c107

c107

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
270.8362976331207, 674.0

c108

c108

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
265.0, 786.0

c109

c109

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
563.4090509434968, 460.0

c11

c11

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
334.9999995550923, 799.903623281043

c110

c110

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
273.2469504755442, 812.0

c111

c111

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
525.923410283849, 590.0

c112

c112

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
518.5777087639997, 598.0

c113

c113

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
518.115466760049, 598.0

c114

c114

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
471.0, 584.0

c115

c115

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
443.0, 609.0

c116

c116

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
472.0, 660.0

c117

c117

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
447.0, 677.0

c118

c118

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
475.0, 720.0

c119

c119

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
312.0, 367.0

c12

c12

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
445.0, 737.0

c120

c120

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
214.15541752799933, 788.0

c121

c121

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
135.64078561329598, 72.99562796168493

c122

c122

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
197.0, 827.0

c123

c123

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
111.84303814972509, 52.68951510544099

c124

c124

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
206.29758237177367, 1026.0

c125

c125

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
200.74662839611992, 1066.0

c126

c126

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
202.50569401612339, 1154.0

c127

c127

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
201.91556182111296, 1113.0

c128

c128

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
193.0, 1219.0

c129

c129

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
327.64990554975276, 400.0

c13

c13

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
203.0, 1084.0

c130

c130

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
193.27838074678232, 1110.0

c131

c131

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
275.0, 1293.0

c132

c132

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
602.0866522822413, 1320.0

c133

c133

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
667.0, 1312.0

c134

c134

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
784.0, 1273.0

c135

c135

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
795.0, 1263.476883547155

c136

c136

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
723.0, 1312.0

c137

c137

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
55.71142534514962, 115.57094042172207

c138

c138

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
630.9861949854, 586.0

c139

c139

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
616.0, 371.0

c14

c14

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
623.0, 601.0

c140

c140

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
572.0, 583.0

c141

c141

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
627.0, 676.0

c142

c142

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
604.0, 691.0

c143

c143

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
564.0, 598.0

c144

c144

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
275.0, 1248.9983134039794

c145

c145

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
275.0, 1264.3318018973807

c146

c146

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
275.0, 1284.2716878491865

c147

c147

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
330.0, 1240.0

c148

c148

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
360.1530859662622, 1212.1192895849365

c149

c149

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
638.4436087949382, 420.0

c15

c15

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
446.0, 1205.9551113054329

c150

c150

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
511.0, 1281.3632612873491

c151

c151

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
432.0, 1228.0

c152

c152

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
496.0, 1246.0

c153

c153

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
625.3892515318946, 1271.6883832866965

c154

c154

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
665.0, 1276.0899458438937

c155

c155

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
265.0, 721.0

c156

c156

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
271.4961229707417, 750.0

c157

c157

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
198.9976215251444, 876.1950639396376

c158

c158

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
193.10251176948293, 797.0

c159

c159

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
555.2221365379228, 528.0

c16

c16

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
191.0, 887.0

c160

c160

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
672.0, 584.0

c161

c161

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
682.5455335748853, 595.0

c162

c162

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
672.0, 597.0

c163

c163

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
684.0, 632.0

c164

c164

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
725.0, 536.0

c165

c165

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
739.0, 632.0

c166

c166

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
709.0, 236.1142740542628

c167

c167

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
806.0, 174.70947270793198

c168

c168

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
312.0, 444.0

c17

c17

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
621.0, 464.0

c18

c18

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
630.3143053269799, 299.2405150182823

c19

c19

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
332.0, 266.0

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
817.0, 262.5777087639997

c20

c20

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
421.0, 249.0

c21

c21

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
573.7611400011626, 362.94028500029066

c22

c22

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
915.7928721853835, 178.0

c23

c23

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
404.0, 480.0

c24

c24

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
728.0, 103.0

c25

c25

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
683.0, 176.0

c26

c26

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
790.0, 199.0

c27

c27

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
743.0, 173.51505822398371

c28

c28

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
869.0, 172.11035345916284

c29

c29

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
584.0, 260.0

c3

c3

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
860.247700587784, 180.0

c30

c30

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
908.0, 259.0

c31

c31

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
406.0, 264.55367983064247

c32

c32

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
412.5876987549066, 264.0

c33

c33

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
413.0, 341.0

c34

c34

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
411.0, 363.2909647972694

c35

c35

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
460.0, 356.0

c36

c36

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
419.0, 521.0

c37

c37

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
982.0, 220.37072939800998

c38

c38

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1055.0, 333.0

c39

c39

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
540.8323146698044, 372.0

c4

c4

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1032.0, 348.0

c40

c40

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
986.9976215251444, 404.0

c41

c41

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
978.0, 420.0

c42

c42

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1020.0, 177.0

c43

c43

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1023.0, 232.0

c44

c44

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1032.0, 296.0

c45

c45

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
986.795129565557, 480.0

c46

c46

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
979.0, 505.0

c47

c47

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
809.8599434057004, 185.1159660434202

c48

c48

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
987.0, 549.0

c49

c49

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
555.0, 372.0

c5

c5

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
978.0, 564.0

c50

c50

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
921.0, 625.0

c51

c51

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
987.0, 625.0

c52

c52

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
976.0, 640.0

c53

c53

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
975.0, 705.0

c54

c54

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
967.0, 719.0

c55

c55

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
975.0, 777.0

c56

c56

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
966.0, 792.0

c57

c57

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
983.0, 861.0

c58

c58

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
919.0, 861.0

c59

c59

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
318.67527876136614, 316.0

c6

c6

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
971.0, 876.0

c60

c60

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1050.0, 624.5381614150846

c61

c61

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
976.0, 1017.0

c62

c62

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1055.2235169765556, 1032.0

c63

c63

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
930.0, 1081.0

c64

c64

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
991.0, 1081.0

c65

c65

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
979.0, 1096.0

c66

c66

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
971.0, 1169.0

c67

c67

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
907.0, 1249.7359593505155

c68

c68

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
956.0, 1244.0

c69

c69

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
333.0, 316.0

c7

c7

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
907.0, 1169.0

c70

c70

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
911.4585460028801, 1184.0

c71

c71

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
907.0, 1229.0

c72

c72

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
711.640365727572, 333.0

c73

c73

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
764.0, 968.0

c74

c74

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
660.0, 992.0

c75

c75

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
654.0, 921.689954939087

c76

c76

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
727.0, 968.8483457221029

c77

c77

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
719.0, 913.0

c78

c78

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
731.2235169765557, 1031.0

c79

c79

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
610.0, 304.0

c8

c8

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
705.0, 297.0

c80

c80

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
713.8784275570199, 330.0

c81

c81

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
758.0301964920179, 328.8178969713206

c82

c82

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
419.0, 465.0

c83

c83

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
464.0, 480.0

c84

c84

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
486.9980180917636, 465.17806348256244

c85

c85

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
555.0, 598.0

c86

c86

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
624.0, 526.0

c87

c87

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
556.0, 855.0

c88

c88

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
624.0, 855.0

c89

c89

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
614.0, 304.0

c9

c9

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
573.0, 939.0

c90

c90

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
559.0, 992.0

c94

c94

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
536.0, 1015.0

c95

c95

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
551.0, 1001.0

c96

c96

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
366.0, 926.375588672083

c97

c97

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
456.90423049601816, 999.3981535963595

c98

c98

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
374.0, 980.0

c99

c99

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back