1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/11207583.csml convertedTime:2009.07.01.10:39

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Pathogen-induced apoptosis of macrophages: a common end for different pathogenicstrategies.
Authors Navarre WW, Zychlinsky A.
Affiliation Skirball Institute for Biomolecular Medicine, Department of Microbiology andKaplan Cancer Center, New York University School of Medicine, NY 10028, USA.
Abstract Microbe-macrophage interactions play a central role in the pathogenesis of manyinfections. Several bacterial pathogens induce apoptosis specifically inmacrophages, but the mechanisms by which it occurs differ, and the resultingpathology can take different courses. Macrophage death caused by Shigellaflexneri and Salmonella spp. has been shown to result in the release ofpro-inflammatory cytokines. Conversely, Yersinia spp. induce apoptosis bysuppressing the signalling pathways that lead to the production of tumournecrosis factor (TNF)-alpha, a cytokine essential for the control of thisinfection. It is likely that there are a variety of reasons why macrophages areparticularly susceptible to pathogen-induced apoptosis. One reason may be theexpression of surface receptors that recognize highly conserved bacterialcomponents, such as lipopolysaccharide (LPS) and bacterial lipoproteins (BLPs).These receptors have recently been shown to activate pro-apoptotic signallingpathways. The roles of macrophage apoptosis in different disease processes arediscussed.
PMID 11207583
Model Abstract

Entity

e1: e10: e11:IpaB:Caspase-1 e12:SipB e13:SipB:Caspase-1 e14:Caspase-11 e15:Caspase-1{active} e16:Il-1beta e17:IL-18 e18:Il-1beta e19:Il-1beta{active} e2: e20:Il-18 e21:Il-18{active} e22:ifn-gamma e23:YopP/J e24:Salmonella e25:Shigella e26:Rho GTPases e27:Rho GTPases{active} e28:MAPK p38 e29:MAPK p38{active} e3: e30:JNK e31:JNK{active} e32:ERK e33:ERK{active} e34:AP-1 e35:AP-1{active} e36:NF-KB e37:NF-KB{active} e38:Calcium e39:Yersinia e4: e40:LPS e41:TLR2 e42:CD14 e43:TLR:CD14 e44:TLR:CD14:LPS e45:cytokines e46:IKBalpha e47:IKBbeta e48:NFKB:IKB e49:MG132 e5:IpaB e50:peptidoglycan e51:Lipoteichoic acids e52:NFKB:IKB{ub} e53:TLR: peptidoglycan e55:TLR:lipoteichoic acid e56:effector e57:NFKB:IKB{p} e6:Caspase-1 e63:protein remnants e64:proteosome e65:NF-KB{active} e66:anti-apoptotic genes e67:MEK{active) e68:YopP/J:MEK{inactive} e69:IKKbeta e7:TNF-alpha e70:BLP e71:TLR2:BLP e72:TLR e73: e74: e75: e76: e77: e78: e79: e8:IL-8 e80: e81: e82: e83: e84: e85: e9:YopP

Process

p1 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p2 p24 p25 p26 p27 p28 p29 p3 p30 p31 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
69.48637070247949, 0.25496770984175043
1002.6878371496139, 1455.9027395412384

--

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
92.49583211255042, 65.29795732584212
975.9363940011215, 1372.8680881043413

--

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
396.5, 180.0
38.58106982169638, 47.242126312281286

IpaB:Caspase-1

--

e11

cso30:c:Complex

cso30:i:CC_Cytosol

--

p1

p5

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
361.5, 265.0
28.101831354397262, 45.57053733145503

SipB

--

e12

cso30:c:Protein

cso30:i:CC_Cytosol

--

p4

p2

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
195.5, 382.0
49.0, 60.0

SipB:Caspase-1

--

e13

cso30:c:Complex

cso30:i:CC_Cytosol

--

p2

p4

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
236.0, 97.5
48.49265445763734, 29.903803582209704

Caspase-11

--

e14

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p3

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
323.0, 451.5
42.71999999999997, 32.04

Caspase-1{active}

--

e15

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
283.0, 1139.0
50.55363321799308, 26.961937716262977

Il-1beta

--

e16

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p6

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
298.0, 1070.0
52.05882352941177, 27.764705882352942

IL-18

--

e17

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

--

p7

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
163.0, 638.5
42.43107265043268, 26.165828134433486

Il-1beta

--

e18

cso30:c:Protein

cso30:i:CC_Cytosol

--

p6

p8

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
1131.0, 636.5
49.9054135640974, 30.7750050311934

Il-1beta{active}

--

e19

cso30:c:Protein

cso30:i:CC_Cytosol

--

p8

--

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
69.48637070247949, 0.25496770984175043
1002.6878371496139, 1455.9027395412384

--

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
580.0, 760.5
48.73415174079291, 30.0527269068223

Il-18

--

e20

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
1132.0, 720.5
48.73415174079291, 30.0527269068223

Il-18{active}

--

e21

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
387.0, 1063.0
50.60553633217993, 26.98961937716263

ifn-gamma

--

e22

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p9 p39 p41 p42

--

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
295.0, 651.0
18.618334892422826, 42.96538821328344

YopP/J

--

e23

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p47 p48

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
570.5, 98.0
34.92103768225714, 51.10395758379095

Salmonella

--

e24

cso30:c:Cell

cso30:i:CC_Cytosol

--

--

p11 p49 p51 p19

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
734.5, 98.0
34.944328725620146, 51.138042037492895

Shigella

--

e25

cso30:c:Cell

cso30:i:CC_Cytosol

--

--

p12

true true true true

csml-variable:Double

m25

0

false

infinite

0

unit false false false

--

Go back
497.0, 279.0
21.67072029934518, 50.00935453695042

Rho GTPases

--

e26

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p11 p12

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
897.0, 131.0
21.67072029934518, 50.00935453695042

Rho GTPases{active}

--

e27

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false false false

--

Go back
501.0, 350.5
45.25659086335278, 27.90823103240088

MAPK p38

--

e28

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p13

true true true true

csml-variable:Double

m28

0

false

infinite

0

unit false false false

--

Go back
588.0, 393.5
47.81646206480176, 29.48681827329442

MAPK p38{active}

--

e29

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
89.54012744547175, 20.308724452834017
962.5803236636295, 1415.795226055254

--

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
677.0, 266.5
45.32904004829945, 27.952908029784663

JNK

--

e30

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p14

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false false false

--

Go back
769.0, 346.5
45.32904004829945, 27.952908029784663

JNK{active}

--

e31

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false false false

--

Go back
842.0, 306.5
43.892131213523854, 27.06681424833971

ERK

--

e32

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p15 p26 p54

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
906.0, 394.5
43.892131213523854, 27.06681424833971

ERK{active}

--

e33

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
420.5, 438.0
22.465083517810427, 36.4298651640169

AP-1

--

e34

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p16 p30 p31

true true true true

csml-variable:Double

m34

0

false

infinite

0

unit false false false

--

Go back
442.0, 499.0
51.34146341463415, 41.073170731707314

AP-1{active}

--

e35

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false false false

--

Go back
458.0, 646.5
35.99999999999998, 26.999999999999996

NF-KB

--

e36

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p36

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false false false

--

Go back
873.0, 909.5
37.59999999999999, 28.2

NF-KB{active}

--

e37

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m37

0

false

infinite

0

unit false false false

--

Go back
941.5, 517.0
28.845925716706684, 29.334839711905094

Calcium

--

e38

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p38

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
1119.5, 922.0
41.0, 60.0

Yersinia

--

e39

cso30:c:Cell

cso30:i:CC_Extracellular

--

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false false false

--

Go back
126.63957742000756, 55.40279875307033
888.3814237145576, 1345.6070774547802

--

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
1109.054667788057, 149.19764507989908
53.31370899915895, 30.211101766190076

LPS

--

e40

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p25

true true true true

csml-variable:Double

m40

0

false

infinite

0

unit false false false

--

Go back
1011.5, 218.0
33.85940246045694, 52.09138840070298

TLR2

--

e41

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p50

true true true true

csml-variable:Double

m41

0

false

infinite

0

unit false false false

--

Go back
1160.0, 23.5
39.436506339303676, 24.319178909237277

CD14

--

e42

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p24

true true true true

csml-variable:Double

m42

0

false

infinite

0

unit false false false

--

Go back
1011.5, 59.0
33.7254987941241, 65.27515895636922

TLR:CD14

--

e43

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m43

0

false

infinite

0

unit false false false

--

Go back
1010.5, 138.0
43.0, 60.0

TLR:CD14:LPS

--

e44

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m44

0

false

infinite

0

unit false false false

--

Go back
332.0, 1007.0
48.9446366782007, 26.103806228373703

cytokines

--

e45

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p35

--

true true true true

csml-variable:Double

m45

0

false

infinite

0

unit false false false

--

Go back
339.0, 526.5
42.41899778627489, 26.15838196820286

IKBalpha

--

e46

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p36

true true true true

csml-variable:Double

m46

0

false

infinite

0

unit false false false

--

Go back
287.5, 591.0
25.763735157979475, 41.77902998591267

IKBbeta

--

e47

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p36

true true true true

csml-variable:Double

m47

0

false

infinite

0

unit false false false

--

Go back
312.5, 722.0
31.352358230868038, 43.74747660121123

NFKB:IKB

--

e48

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m48

0

false

infinite

0

unit false false false

--

Go back
1121.0, 829.0
53.641715727502095, 30.39697224558452

MG132

--

e49

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p58

true true true true

csml-variable:Double

m49

0

false

infinite

0

unit false false false

--

Go back
345.0, 105.5
46.93499698128395, 28.943248138458443

IpaB

--

e5

cso30:c:Protein

cso30:i:CC_Cytosol

--

p5

p1

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
1143.7064760302774, 342.40033641715723
49.04962153069806, 27.794785534062235

peptidoglycan

--

e50

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p52

true true true true

csml-variable:Double

m50

0

false

infinite

0

unit false false false

--

Go back
1152.0, 450.0
48.36837678721616, 27.40874684608915

Lipoteichoic acids

--

e51

cso30:c:SmallMolecule

cso30:i:CC_Extracellular

--

--

p53

true true true true

csml-variable:Double

m51

0

false

infinite

0

unit false false false

--

Go back
831.5, 741.0
32.45714810056892, 45.28904386125896

NFKB:IKB{ub}

--

e52

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m52

0

false

infinite

0

unit false false false

--

Go back
1020.5, 407.0
30.25235693926771, 58.55294891471169

TLR: peptidoglycan

--

e53

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m53

0

false

infinite

0

unit false false false

--

Go back
1020.5, 491.0
30.25235693926771, 58.55294891471169

TLR:lipoteichoic acid

--

e55

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m55

0

false

infinite

0

unit false false false

--

Go back
950.5, 318.0
27.245522237874816, 44.18192795331052

effector

--

e56

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m56

0

false

infinite

0

unit false false false

--

Go back
613.5, 486.0
36.57643604331071, 51.03688750229401

NFKB:IKB{p}

--

e57

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m57

0

false

infinite

0

unit false false false

--

Go back
167.0, 204.5
41.599999999999994, 31.2

Caspase-1

--

e6

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p1 p2 p3

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
959.3911545089028, 888.0781160252728
25.106260769672602, 24.269385410683515

protein remnants

--

e63

cso30:c:EntityBiological

cso30:i:CC_Cytosol

--

p58

--

true true true true

csml-variable:Double

m63

0

false

infinite

0

unit false false false

--

Go back
958.0, 656.0
20.466791393826004, 47.2310570626754

proteosome

--

e64

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p58

true true true true

csml-variable:Double

m64

0

false

infinite

0

unit false false false

--

Go back
661.0, 945.5
37.59999999999999, 28.2

NF-KB{active}

--

e65

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m65

0

false

infinite

0

unit false false false

--

Go back
362.0, 1206.0
52.73356401384083, 28.124567474048444

anti-apoptotic genes

--

e66

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p46

--

true true true true

csml-variable:Double

m66

0

false

infinite

0

unit false false false

--

Go back
193.0, 854.5
45.159991950090564, 27.848661702555848

MEK{active)

--

e67

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p47

true true true true

csml-variable:Double

m67

0

false

infinite

0

unit false false false

--

Go back
270.0, 782.3301469108472
43.51781042463271, 26.83598309519017

YopP/J:MEK{inactive}

--

e68

cso30:c:Protein

cso30:i:CC_NuclearPore

--

p47

--

true true true true

csml-variable:Double

m68

0

false

infinite

0

unit false false false

--

Go back
275.5, 844.0
24.319178909237273, 39.43650633930369

IKKbeta

--

e69

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p48

true true true true

csml-variable:Double

m69

0

false

infinite

0

unit false false false

--

Go back
530.0, 1294.0
52.05882352941177, 27.76470588235294

TNF-alpha

--

e7

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p40 p43 p44

--

true true true true

csml-variable:Double

m7

0

false

infinite

0

unit false false false

--

Go back
1120.0, 203.5
40.70436707587041, 25.10102636345342

BLP

--

e70

cso30:c:Protein

cso30:i:CC_Extracellular

--

--

p50

true true true true

csml-variable:Double

m70

0

false

infinite

0

unit false false false

--

Go back
1012.5, 294.0
31.0, 60.0

TLR2:BLP

--

e71

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

true true true true

csml-variable:Double

m71

0

false

infinite

0

unit false false false

--

Go back
863.5, 18.0
33.85940246045694, 52.09138840070298

TLR

--

e72

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p24 p52 p53

true true true true

csml-variable:Double

m72

0

false

infinite

0

unit false false false

--

Go back
329.45381304491764, 842.6264248332984
343.5258154500719, 516.3827544345035

--

e73

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearPore

--

--

--

true true true true

csml-variable:Double

m73

0

false

infinite

0

unit false true false

--

Go back
430.56284281909575, 1114.607222646587
9.940429445696042, 9.940429445696044

--

e74

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearCentromere

--

--

--

true true true true

csml-variable:Double

m74

0

false

infinite

0

unit false true false

--

Go back
404.4692155241427, 1066.7689059391732
18.60509664905742, 8.958009497694325

--

e75

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Chromatin

--

--

--

true true true true

csml-variable:Double

m75

0

false

infinite

0

unit false true false

--

Go back
403.8479386837868, 1040.0540018038657
63.680876136490284, 114.62557704568252

--

e76

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearChromosome

--

--

--

true true true true

csml-variable:Double

m76

0

false

infinite

0

unit false true false

--

Go back
266.0, 830.0
587.4947862951869, 532.7932233254306

--

e77

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearOuterMembrane

--

--

--

true true true true

csml-variable:Double

m77

0

false

infinite

0

unit false true false

--

Go back
694.860253682892, 1048.8062518790264
36.70344625522661, 33.2262776626262

--

e78

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearBody

--

--

--

true true true true

csml-variable:Double

m78

0

false

infinite

0

unit false true false

--

Go back
273.65821881576596, 837.1112031860685
572.1783486636554, 518.5708169532933

--

e79

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearInnerMembrane

--

--

--

true true true true

csml-variable:Double

m79

0

false

infinite

0

unit false true false

--

Go back
467.0, 1127.0
50.03460207612457, 26.685121107266433

IL-8

--

e8

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p49 p51

--

true true true true

csml-variable:Double

m8

0

false

infinite

0

unit false false false

--

Go back
274.7522500751611, 838.205234445463
569.9902861448644, 516.3827544345035

--

e80

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearLumen

--

--

--

true true true true

csml-variable:Double

m80

0

false

infinite

0

unit false true false

--

Go back
274.7522500751611, 838.205234445463
569.9902861448644, 516.3827544345035

--

e81

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleoplasm

--

--

--

true true true true

csml-variable:Double

m81

0

false

infinite

0

unit false true false

--

Go back
598.5855028561209, 1201.9706281943459
103.93296964253767, 94.08668830798162

--

e82

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleolus

--

--

--

true true true true

csml-variable:Double

m82

0

false

infinite

0

unit false true false

--

Go back
266.0, 830.0
587.4947862951869, 532.7932233254306

--

e83

cso30:c:EntityBiologicalCompartment

cso30:i:CC_Nucleus

--

--

--

true true true true

csml-variable:Double

m83

0

false

infinite

0

unit false true false

--

Go back
266.0, 830.0
587.4947862951869, 532.7932233254306

--

e84

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelopeLumen

--

--

--

true true true true

csml-variable:Double

m84

0

false

infinite

0

unit false true false

--

Go back
266.0, 830.0
587.4947862951869, 532.7932233254306

--

e85

cso30:c:EntityBiologicalCompartment

cso30:i:CC_NuclearEnvelope

--

--

--

true true true true

csml-variable:Double

m85

0

false

infinite

0

unit false true false

--

Go back
862.0, 1225.0
20.101964452759585, 46.38914873713751

YopP

--

e9

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m9

0

false

infinite

0

unit false false false

--

Go back
265.0, 261.0
30.0, 30.0

p1

p1

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m5*m6*0.1

nodelay

--

true

0

false

PMID: 11207583, 8670890, 10051653 However, compelling evidence has emerged that IpaB and SipB are directly responsible for triggering apoptosis in macrophages through their ability to bind Caspase-1 (interleukin-1¦Â converting enzyme; ICE), a member of the pro-apoptotic family of cysteine proteases ( Chen et al., 1996b; Hersh et al., 1999).

Go back
817.0, 813.0
30.0, 30.0

p10

p10

cso30:i:ME_Cleavage

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c23 : 1
stoichiometry:c24 : 1
stoichiometry:c25 : 1

m15*m20*0.1

nodelay

--

true

0

false

PMID: 11207583, 1574116 An important consequence of Caspase-1 activation is the processing and release of the pro-inflammatory cytokines interleukin (IL)-1¦Â and IL-18. These cytokines are synthesized as inactive precursors in the cytosol of macrophages and are proteolytically converted to their mature, active form by Caspase-1

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529.0, 201.0
30.0, 30.0

p11

p11

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c29 : 1
stoichiometry:c30 : 1
stoichiometry:c31 : 1

m24*m26*0.1

nodelay

--

true

0

false

PMID: 11207583, 9630225, 10362537 Salmonella and Shigella initiate the intracellular invasion process through the activation of the small Rho GTPases, which can induce localized actin rearrangements at the plasma membrane

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617.0, 165.0
30.0, 30.0

p11

p12

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c32 : 1
stoichiometry:c33 : 1
stoichiometry:c34 : 1

m25*m26*0.1

nodelay

--

true

0

false

PMID: 11207583, 9630225, 10362537 Salmonella and Shigella initiate the intracellular invasion process through the activation of the small Rho GTPases, which can induce localized actin rearrangements at the plasma membrane

Go back
613.0, 249.0
30.0, 30.0

p13

p13

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c35 : 1
stoichiometry:c38 : 1
stoichiometry:c169 : 1
stoichiometry:c39 : 1

m27*m28*0.1

nodelay

--

true

0

false

PMID: 11207583, 9548496, 8953049, 10224288 Activation of these GTPases stimulates the mitogen-activated protein kinases (MAPKs) p38, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) PMID: 11207583, 9535085, 9188492 Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-¦Ã and TNF-¦Á

Go back
781.0, 233.0
30.0, 30.0

p13

p14

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c36 : 1
stoichiometry:c40 : 1
stoichiometry:c168 : 1
stoichiometry:c41 : 1

m27*m30*0.1

nodelay

--

true

0

false

PMID: 11207583, 9548496, 8953049, 10224288 Activation of these GTPases stimulates the mitogen-activated protein kinases (MAPKs) p38, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) PMID: 11207583, 9535085, 9188492 Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-¦Ã and TNF-¦Á

Go back
849.0, 233.0
30.0, 30.0

p13

p15

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c37 : 1
stoichiometry:c42 : 1
stoichiometry:c166 : 1
stoichiometry:c43 : 1

m27*m32*0.1

nodelay

--

true

0

false

PMID: 11207583, 9548496, 8953049, 10224288 Activation of these GTPases stimulates the mitogen-activated protein kinases (MAPKs) p38, c-Jun N-terminal kinase (JNK) and extracellular signal-regulated kinase (ERK) PMID: 11207583, 9535085, 9188492 Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-¦Ã and TNF-¦Á

Go back
506.0, 410.0
27.0, 27.0

p16

p16

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c44 : 1
stoichiometry:c45 : 1
stoichiometry:c46 : 1

m29*m34*0.1

nodelay

--

true

0

false

PMID: 11207583, 9548496 Activation of these MAPK signalling cascades by Salmonella leads to the phosphorylation and activation of the transcription factor AP-1

Go back
762.0, 658.0
28.0, 28.0

p17

p17

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c47 : 1
stoichiometry:c103 : 1

m48*0.1

nodelay

--

true

0

false

PMID:11207583, 10488062 Before activation, the NF-¦ÊB transcription factor is sequestered within the cytoplasm by its interaction with two I¦ÊB ( Inhibitors of NF- ¦ÊB) proteins, I¦ÊB¦Á and I¦ÊB¦Â (for a review, see Karin, 1999). The I¦ÊB proteins bind to and prevent the recognition of NF-¦ÊB nuclear localization signals. Phosphorylation of the I¦ÊB proteins results in their targeted degradation by the ubiquitin/proteasome pathway, thereby enabling NF-¦ÊB to translocate to the nucleus and activate transcription

Go back
905.0, 673.0
29.0, 29.0

p18

p18

cso30:i:ME_Ubiquitination

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c49 : 1
stoichiometry:c157 : 1

m57*0.1

nodelay

--

true

0

false

PMID:11207583, 10488062 Before activation, the NF-¦ÊB transcription factor is sequestered within the cytoplasm by its interaction with two I¦ÊB ( Inhibitors of NF- ¦ÊB) proteins, I¦ÊB¦Á and I¦ÊB¦Â (for a review, see Karin, 1999). The I¦ÊB proteins bind to and prevent the recognition of NF-¦ÊB nuclear localization signals. Phosphorylation of the I¦ÊB proteins results in their targeted degradation by the ubiquitin/proteasome pathway, thereby enabling NF-¦ÊB to translocate to the nucleus and activate transcription Inhibition of the proteasome with specific inhibitors (MG132) results in the inhibition of NF-¦ÊB nuclear translocation, even in the presence of the proper activating stimuli. PMID: 11207583, 9529323 This hypothesis is supported by the finding that the inhibition of NF-kB activation by the proteasome inhibitor MG-132 enables both LPS and plasmid-cured Yersinia to induce apoptosis in J774 macrophages (Ruckdeschel et al., 1998).

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725.0, 193.0
30.0, 30.0

p19

p19

cso30:i:ME_Translocation

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c56 : 1
stoichiometry:c53 : 1

m24*0.1

nodelay

--

true

0

false

PMID: 11207583 The results indicate that LPS alone is sufficient to stimulate the ERK kinase in macrophages, whereas ERK activation requires an effector from the Salmonella type III secretion system in epithelial cells

Go back
205.0, 301.0
30.0, 30.0

p2

p2

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c4 : 1
stoichiometry:c5 : 1
stoichiometry:c6 : 1

m12*m6*0.1

nodelay

--

true

0

false

PMID: 11207583, 8670890, 10051653 However, compelling evidence has emerged that IpaB and SipB are directly responsible for triggering apoptosis in macrophages through their ability to bind Caspase-1 (interleukin-1¦Â converting enzyme; ICE), a member of the pro-apoptotic family of cysteine proteases ( Chen et al., 1996b; Hersh et al., 1999).

Go back
1087.0, 15.0
25.0, 25.0

p24

p24

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c63 : 1
stoichiometry:c138 : 1
stoichiometry:c65 : 1

m42*m72*0.1

nodelay

--

true

0

false

PMID: 11207583, 9363937, 9751057 CD14 co-operates with the recently identified family of Toll-like receptors (TLRs) in the recognition of conserved bacterial molecules or ¡Æpathogen-associated microbial patterns¡Ç (PAMPs)

Go back
1114.0, 74.0
27.0, 27.0

p25

p25

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c66 : 1
stoichiometry:c67 : 1
stoichiometry:c68 : 1

m43*m40*0.1

nodelay

--

true

0

false

PMID: 11207583, 9363937, 9751057 CD14 co-operates with the recently identified family of Toll-like receptors (TLRs) in the recognition of conserved bacterial molecules or ¡Æpathogen-associated microbial patterns¡Ç (PAMPs)

Go back
921.0, 201.0
29.0, 29.0

p26

p26

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c69 : 1
stoichiometry:c70 : 1
stoichiometry:c167 : 1
stoichiometry:c71 : 1

m44*m32*0.1

nodelay

--

true

0

false

PMID: 11207583 The results indicate that LPS alone is sufficient to stimulate the ERK kinase in macrophages, whereas ERK activation requires an effector from the Salmonella type III secretion system in epithelial cells PMID: 11207583, 9535085, 9188492 Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-¦Ã and TNF-¦Á

Go back
712.0, 688.0
23.0, 23.0

p28

p27

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c72 : 1
stoichiometry:c76 : 1
stoichiometry:c100 : 1

m55*m48*0.1

nodelay

--

true

0

false

PMID: 11207583, 9237759, 9734363 Stimulation of TLRs with their cognate PAMPs is known to activate NF-¦ÊB through the phosphorylation of the I¦ÊB proteins

Go back
508.0, 536.0
23.0, 23.0

p28

p28

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c74 : 1
stoichiometry:c75 : 1
stoichiometry:c153 : 1

m29*m48*0.1

nodelay

--

true

0

false

PMID: 11207583, 9689033 Like AP-1, NF-¦ÊB can also be activated by MAPK pathways

Go back
548.0, 616.0
23.0, 23.0

p28

p29

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c78 : 1
stoichiometry:c79 : 1
stoichiometry:c77 : 1

m31*m48*0.1

nodelay

--

true

0

false

PMID: 11207583, 9689033 Like AP-1, NF-¦ÊB can also be activated by MAPK pathways

Go back
267.0, 179.0
25.0, 25.0

p3

p3

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c7 : 1
stoichiometry:c8 : 1
stoichiometry:c9 : 1

m14*m6*0.1

nodelay

--

true

0

false

PMID: 11207583, 9491891 Shigella-induced apoptosis does not require either Caspase-11, a caspase thought to be required for the activation of Caspase-1

Go back
660.0, 412.0
23.0, 23.0

p30

p30

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m31*m34*0.1

nodelay

--

true

0

false

PMID: 11207583, 9548496 Activation of these MAPK signalling cascades by Salmonella leads to the phosphorylation and activation of the transcription factor AP-1

Go back
784.0, 420.0
23.0, 23.0

p30

p31

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m33*m34*0.1

nodelay

--

true

0

false

PMID: 11207583, 9548496 Activation of these MAPK signalling cascades by Salmonella leads to the phosphorylation and activation of the transcription factor AP-1

Go back
567.0, 895.0
25.0, 25.0

p9

p35

cso30:i:ME_GeneExpression

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c124 : 1
stoichiometry:c95 : 1

m65*0.1

nodelay

--

true

0

false

PMID: 11207583, 9081673 In addition to its role in activating cytokine expression, NF-¦ÊB can suppress apoptosis at least in part through the activation of several anti-apoptotic genes

Go back
391.0, 599.0
25.0, 25.0

p36

p36

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c96 : 1
stoichiometry:c97 : 1
stoichiometry:c98 : 1
stoichiometry:c99 : 1

m46*m47*m36*0.1

nodelay

--

true

0

false

PMID:11207583, 10488062 Before activation, the NF-¦ÊB transcription factor is sequestered within the cytoplasm by its interaction with two I¦ÊB ( Inhibitors of NF- ¦ÊB) proteins, I¦ÊB¦Á and I¦ÊB¦Â (for a review, see Karin, 1999). The I¦ÊB proteins bind to and prevent the recognition of NF-¦ÊB nuclear localization signals. Phosphorylation of the I¦ÊB proteins results in their targeted degradation by the ubiquitin/proteasome pathway, thereby enabling NF-¦ÊB to translocate to the nucleus and activate transcription

Go back
612.0, 672.0
23.0, 23.0

p28

p37

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c101 : 1
stoichiometry:c102 : 1
stoichiometry:c48 : 1

m33*m48*0.1

nodelay

--

true

0

false

PMID: 11207583, 9689033 Like AP-1, NF-¦ÊB can also be activated by MAPK pathways

Go back
640.0, 604.0
23.0, 23.0

p28

p38

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c106 : 1
stoichiometry:c107 : 1
stoichiometry:c154 : 1

m38*m48*0.1

nodelay

--

true

0

false

PMID: 11207583, 10619864 This hypothesis has recently been complicated by evidence that Salmonella-induced NF-¦ÊB activation in epithelial cells occurs via a calcium-mediated signalling event

Go back
375.0, 955.0
25.0, 25.0

p9

p39

cso30:i:ME_GeneExpression

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c110 : 1
stoichiometry:c62 : 1
stoichiometry:c111 : 1

m29*0.1

nodelay

--

true

0

false

PMID: 11207583, 9535085, 9188492 Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-¦Ã and TNF-¦Á PMID: 11207583, 1287419, 8418045 It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-¦Ã and TNF-¦Á and that this inhibition is required for bacterial survival in animal models

Go back
433.0, 365.0
30.0, 30.0

p4

p4

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c11 : 1
stoichiometry:c14 : 1
stoichiometry:c15 : 1

m13*0.1

nodelay

--

true

0

false

PMID: 11207583 These findings have led to the hypothesis that delivery of IpaB/SipB to the macrophage cytosol stimulates the activation of Caspase-1, leading to the activation of the apoptotic machinery and, ultimately, the demise of the macrophage

Go back
515.0, 1195.0
25.0, 25.0

p9

p40

cso30:i:ME_GeneExpression

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c117 : 1
stoichiometry:c61 : 1
stoichiometry:c163 : 1
stoichiometry:c120 : 1

m31*0.1

nodelay

--

true

0

false

PMID: 11207583, 9535085, 9188492 Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-¦Ã and TNF-¦Á PMID: 11207583, 1287419, 8418045 It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-¦Ã and TNF-¦Á and that this inhibition is required for bacterial survival in animal models PMID:11207583, 9356502, 9294220, 9680199, 9916081 It has been demonstrated that a single bacterial protein, YopP of Y. enterocolitica (YopJ in Y. pseudotuberculosis), is required for inducing apoptosis in macrophages and is sufficient to suppress the expression of TNF-¦Á and IL-8

Go back
427.0, 931.0
25.0, 25.0

p9

p41

cso30:i:ME_GeneExpression

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c112 : 1
stoichiometry:c60 : 1
stoichiometry:c114 : 1

m31*0.1

nodelay

--

true

0

false

PMID: 11207583, 9535085, 9188492 Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-¦Ã and TNF-¦Á PMID: 11207583, 1287419, 8418045 It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-¦Ã and TNF-¦Á and that this inhibition is required for bacterial survival in animal models

Go back
523.0, 907.0
25.0, 25.0

p9

p42

cso30:i:ME_GeneExpression

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c113 : 1
stoichiometry:c58 : 1
stoichiometry:c115 : 1

m33*0.1

nodelay

--

true

0

false

PMID: 11207583, 9535085, 9188492 Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-¦Ã and TNF-¦Á PMID: 11207583, 1287419, 8418045 It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-¦Ã and TNF-¦Á and that this inhibition is required for bacterial survival in animal models

Go back
587.0, 1187.0
25.0, 25.0

p9

p43

cso30:i:ME_GeneExpression

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c118 : 1
stoichiometry:c161 : 1
stoichiometry:c164 : 1
stoichiometry:c121 : 1

m33*0.1

nodelay

--

true

0

false

PMID: 11207583, 9535085, 9188492 Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-¦Ã and TNF-¦Á PMID: 11207583, 1287419, 8418045 It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-¦Ã and TNF-¦Á and that this inhibition is required for bacterial survival in animal models PMID:11207583, 9356502, 9294220, 9680199, 9916081 It has been demonstrated that a single bacterial protein, YopP of Y. enterocolitica (YopJ in Y. pseudotuberculosis), is required for inducing apoptosis in macrophages and is sufficient to suppress the expression of TNF-¦Á and IL-8

Go back
427.0, 1203.0
25.0, 25.0

p9

p44

cso30:i:ME_GeneExpression

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c116 : 1
stoichiometry:c59 : 1
stoichiometry:c162 : 1
stoichiometry:c119 : 1

m29*0.1

nodelay

--

true

0

false

PMID: 11207583, 9535085, 9188492 Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-¦Ã and TNF-¦Á PMID: 11207583, 1287419, 8418045 It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-¦Ã and TNF-¦Á and that this inhibition is required for bacterial survival in animal models PMID:11207583, 9356502, 9294220, 9680199, 9916081 It has been demonstrated that a single bacterial protein, YopP of Y. enterocolitica (YopJ in Y. pseudotuberculosis), is required for inducing apoptosis in macrophages and is sufficient to suppress the expression of TNF-¦Á and IL-8

Go back
796.0, 900.0
23.0, 23.0

p45

p45

cso30:i:ME_Translocation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c94 : 1
stoichiometry:c123 : 1

m37*0.1

nodelay

--

true

0

false

PMID:11207583, 10488062 Before activation, the NF-¦ÊB transcription factor is sequestered within the cytoplasm by its interaction with two I¦ÊB ( Inhibitors of NF- ¦ÊB) proteins, I¦ÊB¦Á and I¦ÊB¦Â (for a review, see Karin, 1999). The I¦ÊB proteins bind to and prevent the recognition of NF-¦ÊB nuclear localization signals. Phosphorylation of the I¦ÊB proteins results in their targeted degradation by the ubiquitin/proteasome pathway, thereby enabling NF-¦ÊB to translocate to the nucleus and activate transcription

Go back
376.0, 1132.0
23.0, 23.0

p46

p46

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c125 : 1
stoichiometry:c126 : 1

m65*0.1

nodelay

--

true

0

false

PMID: 11207583, 9081673 In addition to its role in activating cytokine expression, NF-¦ÊB can suppress apoptosis at least in part through the activation of several anti-apoptotic genes

Go back
217.0, 725.0
21.0, 21.0

p47

p47

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c127 : 1
stoichiometry:c128 : 1
stoichiometry:c129 : 1

m23*m67*0.1

nodelay

--

true

0

false

PMID: 11207583, 10489373 A recent report demonstrated that YopP/J binds to and prevents the activation of members of the MAP kinase kinase (MEK) superfamily (

Go back
710.0, 746.0
27.0, 27.0

p48

p48

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c130 : 1
stoichiometry:c131 : 1
stoichiometry:c134 : 1
stoichiometry:c73 : 1

m69*m48*0.1

nodelay

--

true

0

false

PMID: 11207583, 9529323, 9680199 The curious connection between the ability to suppress the synthesis of cytokines and the induction of apoptosis appears to hinge on the ability of YopP/J to inhibit the activation of the NF-¦ÊB transcription factor PMID: 11207583, 9529323, 9680199, 10489373 One member of this family is I¦ÊB-kinase ¦Â (IKK¦Â), a protein implicated in the activation of NF-¦ÊB via phosphorylation of I¦ÊBs. Indeed, NF-¦ÊB activation is impaired in both macrophages and epithelial cells infected with wild-type but not YopP/J mutant Yersinia

Go back
531.0, 1063.0
25.0, 25.0

p19

p49

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c139 : 1
stoichiometry:c142 : 1
stoichiometry:c52 : 1
stoichiometry:c57 : 1
stoichiometry:c140 : 1

m24*m35*0.1

nodelay

--

true

0

false

PMID: 11207583, 9548496, 10415047 The induction of the chemokine IL-8 by Salmonella has been relatively well studied and requires the transcription factors NF-¦ÊB and AP-1 PMID: 11207583, 1287419, 8418045 It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-¦Ã and TNF-¦Á and that this inhibition is required for bacterial survival in animal models PMID:11207583, 9356502, 9294220, 9680199, 9916081 It has been demonstrated that a single bacterial protein, YopP of Y. enterocolitica (YopJ in Y. pseudotuberculosis), is required for inducing apoptosis in macrophages and is sufficient to suppress the expression of TNF-¦Á and IL-8

Go back
473.0, 121.0
30.0, 30.0

p5

p5

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c13 : 1
stoichiometry:c12 : 1

m11*0.1

nodelay

--

true

0

false

PMID: 11207583 These findings have led to the hypothesis that delivery of IpaB/SipB to the macrophage cytosol stimulates the activation of Caspase-1, leading to the activation of the apoptotic machinery and, ultimately, the demise of the macrophage

Go back
1091.0, 267.0
25.0, 25.0

p50

p50

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

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

m70*m41*0.1

nodelay

--

true

0

false

PMID: 11207583 Examples of PAMPs include LPS, BLPs, peptidoglycan and lipoteichoic acids. PMID: 11207583 It has been shown that BLPs are the ligands for TLR-2

Go back
599.0, 1075.0
25.0, 25.0

p19

p51

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c64 : 1
stoichiometry:c143 : 1
stoichiometry:c160 : 1
stoichiometry:c54 : 1
stoichiometry:c141 : 1

m24*m65*0.1

nodelay

--

true

0

false

PMID: 11207583, 9548496, 10415047 The induction of the chemokine IL-8 by Salmonella has been relatively well studied and requires the transcription factors NF-¦ÊB and AP-1 PMID: 11207583, 1287419, 8418045 It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-¦Ã and TNF-¦Á and that this inhibition is required for bacterial survival in animal models PMID:11207583, 9356502, 9294220, 9680199, 9916081 It has been demonstrated that a single bacterial protein, YopP of Y. enterocolitica (YopJ in Y. pseudotuberculosis), is required for inducing apoptosis in macrophages and is sufficient to suppress the expression of TNF-¦Á and IL-8

Go back
1109.0, 385.0
21.0, 21.0

p52

p52

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c145 : 1
stoichiometry:c144 : 1
stoichiometry:c146 : 1

m50*m72*0.1

nodelay

--

true

0

false

PMID: 11207583 Examples of PAMPs include LPS, BLPs, peptidoglycan and lipoteichoic acids.

Go back
1117.0, 497.0
21.0, 21.0

p52

p53

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c148 : 1
stoichiometry:c147 : 1
stoichiometry:c149 : 1

m51*m72*0.1

nodelay

--

true

0

false

PMID: 11207583 Examples of PAMPs include LPS, BLPs, peptidoglycan and lipoteichoic acids.

Go back
863.0, 355.0
25.0, 25.0

p54

p54

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c150 : 1
stoichiometry:c151 : 1
stoichiometry:c165 : 1
stoichiometry:c152 : 1

m56*m32*0.1

nodelay

--

true

0

false

PMID: 11207583 The results indicate that LPS alone is sufficient to stimulate the ERK kinase in macrophages, whereas ERK activation requires an effector from the Salmonella type III secretion system in epithelial cells PMID: 11207583, 9535085, 9188492 Recently, it has been demonstrated that this inhibition correlates with the ability of Yersinia to suppress the MAP kinase pathways that are involved in the induction of various pro-inflammatory molecules, including IFN-¦Ã and TNF-¦Á

Go back
828.0, 700.0
23.0, 23.0

p28

p55

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c104 : 1
stoichiometry:c105 : 1
stoichiometry:c108 : 1

m53*m48*0.1

nodelay

--

true

0

false

PMID: 11207583, 9237759, 9734363 Stimulation of TLRs with their cognate PAMPs is known to activate NF-¦ÊB through the phosphorylation of the I¦ÊB proteins

Go back
776.0, 580.0
23.0, 23.0

p28

p56

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c109 : 1
stoichiometry:c122 : 1
stoichiometry:c132 : 1

m71*m48*0.1

nodelay

--

true

0

false

PMID: 11207583, 9237759, 9734363 Stimulation of TLRs with their cognate PAMPs is known to activate NF-¦ÊB through the phosphorylation of the I¦ÊB proteins

Go back
864.0, 576.0
23.0, 23.0

p28

p57

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c133 : 1
stoichiometry:c155 : 1
stoichiometry:c156 : 1

m44*m48*0.1

nodelay

--

true

0

false

PMID: 11207583, 9237759, 9734363 Stimulation of TLRs with their cognate PAMPs is known to activate NF-¦ÊB through the phosphorylation of the I¦ÊB proteins

Go back
902.0, 758.0
27.0, 27.0

p58

p58

cso30:i:ME_UnknownDegradation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c158 : 1
stoichiometry:c28 : 1
stoichiometry:c50 : 1
stoichiometry:c159 : 1
stoichiometry:c51 : 1

m52*m64*0.1

nodelay

--

true

0

false

PMID:11207583, 10488062 Before activation, the NF-¦ÊB transcription factor is sequestered within the cytoplasm by its interaction with two I¦ÊB ( Inhibitors of NF- ¦ÊB) proteins, I¦ÊB¦Á and I¦ÊB¦Â (for a review, see Karin, 1999). The I¦ÊB proteins bind to and prevent the recognition of NF-¦ÊB nuclear localization signals. Phosphorylation of the I¦ÊB proteins results in their targeted degradation by the ubiquitin/proteasome pathway, thereby enabling NF-¦ÊB to translocate to the nucleus and activate transcription Inhibition of the proteasome with specific inhibitors (MG132) results in the inhibition of NF-¦ÊB nuclear translocation, even in the presence of the proper activating stimuli. PMID: 11207583, 9529323 This hypothesis is supported by the finding that the inhibition of NF-kB activation by the proteasome inhibitor MG-132 enables both LPS and plasmid-cured Yersinia to induce apoptosis in J774 macrophages (Ruckdeschel et al., 1998).

Go back
157.0, 1009.0
30.0, 30.0

p6

p6

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m16*0.1

nodelay

--

true

0

false

PMID: 11207583, 1574116 An important consequence of Caspase-1 activation is the processing and release of the pro-inflammatory cytokines interleukin (IL)-1¦Â and IL-18. These cytokines are synthesized as inactive precursors in the cytosol of macrophages and are proteolytically converted to their mature, active form by Caspase-1

Go back
337.0, 785.0
30.0, 30.0

p6

p7

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c17 : 1
stoichiometry:c22 : 1

m17*0.1

nodelay

--

true

0

false

PMID: 11207583, 1574116 An important consequence of Caspase-1 activation is the processing and release of the pro-inflammatory cytokines interleukin (IL)-1¦Â and IL-18. These cytokines are synthesized as inactive precursors in the cytosol of macrophages and are proteolytically converted to their mature, active form by Caspase-1

Go back
225.0, 545.0
30.0, 30.0

p8

p8

cso30:i:ME_Cleavage

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m15*m18*0.1

nodelay

--

true

0

false

PMID: 11207583, 1574116 An important consequence of Caspase-1 activation is the processing and release of the pro-inflammatory cytokines interleukin (IL)-1¦Â and IL-18. These cytokines are synthesized as inactive precursors in the cytosol of macrophages and are proteolytically converted to their mature, active form by Caspase-1

Go back
551.0, 967.0
25.0, 25.0

p9

p9

cso30:i:ME_GeneExpression

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c26 : 1
stoichiometry:c55 : 1
stoichiometry:c27 : 1

m21*0.1

nodelay

--

true

0

false

PMID: 11207583 One role of IL-18 is to augment the induction of interferon (IFN)-¦Ã, a cytokine produced mainly by T-cells and non-killer (NK) cells. PMID: 11207583, 1287419, 8418045 It has also been demonstrated that Yersinia is capable of inhibiting the expression of IL-8, IFN-¦Ã and TNF-¦Á and that this inhibition is required for bacterial survival in animal models

Go back
291.9454831315887, 134.0

c1

c1

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
435.0, 155.50195718328627

c10

c10

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
647.5205056107437, 544.1837344219231

c100

c100

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
640.9272325009983, 422.0

c101

c101

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
344.0, 687.6082726455269

c102

c102

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
655.3412636682482, 537.955745329197

c103

c103

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
853.6345994142182, 458.0

c104

c104

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
344.0, 713.4949179548167

c105

c105

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
670.7116965589678, 536.0

c106

c106

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
344.0, 623.9407655917186

c107

c107

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
655.7691551734786, 534.542278284634

c108

c108

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
804.3365453111925, 341.0

c109

c109

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
245.0, 383.1372674787471

c11

c11

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
395.9735321936421, 423.0

c110

c110

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
391.0, 980.0

c111

c111

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
452.1232037928378, 374.0

c112

c112

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
550.8688260885667, 422.0

c113

c113

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
416.61115694427014, 956.0

c114

c114

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
426.9741944072455, 932.0

c115

c115

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
444.66526954841066, 423.0

c116

c116

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
534.3729498269439, 374.0

c117

c117

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
608.0625115903847, 422.0

c118

c118

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
452.0, 1226.0

c119

c119

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
399.9272356814489, 124.0765381789622

c12

c12

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
531.0, 1220.0

c120

c120

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
564.9867234701101, 1212.0

c121

c121

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
344.0, 598.5139942887765

c122

c122

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
706.5001229944764, 917.0

c123

c123

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
599.0926787693236, 917.7005280535601

c124

c124

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
405.7694312146167, 972.0

c125

c125

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
388.0, 1155.0

c126

c126

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
244.1192895849364, 680.0

c127

c127

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
217.0, 753.9665438480602

c128

c128

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
238.0, 745.0

c129

c129

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
354.171955509671, 151.0

c13

c13

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
300.0, 764.8598052138072

c130

c130

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
344.0, 745.0

c131

c131

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
657.1097069516725, 524.6677059671326

c132

c132

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
882.7959447706688, 198.0

c133

c133

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
314.0, 674.0

c134

c134

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1045.0, 252.0

c135

c135

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1115.0082901643336, 229.0

c136

c136

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1050.9368443397661, 288.0

c137

c137

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
897.0, 29.58787993778281

c138

c138

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
545.367227370326, 149.0

c139

c139

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
394.86745234925706, 311.3488508903353

c14

c14

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
507.97795300460297, 1088.0

c140

c140

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
524.3577934305443, 1094.0

c141

c141

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
471.0, 540.0

c142

c142

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
622.7719548666504, 974.0

c143

c143

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
897.0, 70.0

c144

c144

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1136.0955145420758, 370.0

c145

c145

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1058.2044130909167, 401.0

c146

c146

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
894.0, 70.0

c147

c147

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1143.7811348571815, 477.0

c148

c148

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1058.9266413443545, 509.0

c149

c149

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
370.08026870758346, 393.0

c15

c15

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
895.6249941371564, 344.0

c150

c150

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
867.0, 334.0

c151

c151

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
888.0, 377.0

c152

c152

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
531.0, 520.3914365841244

c153

c153

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
638.5238197468426, 544.8535325414193

c154

c154

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
344.0, 593.1899506244386

c155

c155

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
657.6446856505135, 520.3577067894107

c156

c156

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
869.5268621723706, 702.0

c157

c157

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
864.0, 766.0

c158

c158

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
895.2639240088533, 785.0

c159

c159

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
192.81761282122181, 1043.491391541527

c16

c16

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
627.8731092948374, 957.0

c160

c160

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
615.6358073467, 961.0

c161

c161

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
455.98933489436627, 1217.2919025532462

c162

c162

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
543.9724337395459, 1209.4687965282694

c163

c163

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
615.9394510962156, 1202.693343392934

c164

c164

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
882.647608078991, 383.6449125665842

c165

c165

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
871.4582367065213, 266.72472088991293

c166

c166

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
941.0694263105219, 233.8543906608391

c167

c167

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
804.7560579855148, 266.5939199144541

c168

c168

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
641.3912413719403, 282.2065502804605

c169

c169

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
325.0, 822.9587374407893

c17

c17

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
173.0, 672.9959130852482

c18

c18

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
261.020613557655, 484.0

c19

c19

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
209.0, 233.0

c2

c2

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
192.0, 581.831526369483

c20

c20

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
255.0, 561.0

c21

c21

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
367.0, 778.7849267606894

c22

c22

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
365.0, 484.0

c23

c23

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
629.0, 782.0

c24

c24

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
847.0, 745.187068449479

c25

c25

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
583.3971492262416, 746.0

c26

c26

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
439.7516468948037, 988.0

c27

c27

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
932.8179199121402, 777.1930999725438

c28

c28

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
554.466355478943, 149.0

c29

c29

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
295.0, 217.74310176335226

c3

c3

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
518.0, 238.3846153846154

c30

c30

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
559.0, 159.30761821432915

c31

c31

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
654.2515689329545, 132.0

c32

c32

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
519.0, 200.65685424949237

c33

c33

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
647.0, 157.70128984247611

c34

c34

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
650.4637313378096, 160.0

c35

c35

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
817.1692251595242, 165.0

c36

c36

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
874.4705249501832, 179.0

c37

c37

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
538.0, 284.5402546255177

c38

c38

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
614.8302746369562, 279.0

c39

c39

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
242.88260338367064, 291.0

c4

c4

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
722.0, 255.56831424926318

c40

c40

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
792.2855322440993, 263.0

c41

c41

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
864.0, 271.0

c42

c42

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
870.0, 263.0

c43

c43

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
540.8709592807993, 412.0

c44

c44

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
443.0, 431.74351979122076

c45

c45

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
482.8466608896548, 437.0

c46

c46

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
344.0, 675.2661350597559

c47

c47

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
625.0, 544.9921104517297

c48

c48

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
650.0, 523.0

c49

c49

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
193.0, 236.0

c5

c5

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
927.9441005758471, 698.0

c50

c50

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
922.0, 785.0

c51

c51

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
559.9152272318285, 956.0

c52

c52

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
755.0, 217.0

c53

c53

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
627.4031919894371, 1097.1019715228877

c54

c54

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
579.9954392566542, 953.0

c55

c55

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
605.0, 134.0

c56

c56

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
559.5399237983804, 1083.8625089265988

c57

c57

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
551.9945098324331, 921.2095022639388

c58

c58

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
455.7443944717716, 960.0

c59

c59

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
220.0, 331.0

c6

c6

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
455.9997131794059, 944.0479007566396

c60

c60

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
543.6915540251235, 961.0

c61

c61

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
403.99901271132643, 952.0

c62

c62

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
1119.9569472711262, 29.82884867407565

c63

c63

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
589.0, 149.0

c64

c64

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1051.0028719586805, 40.0

c65

c65

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1045.0, 89.23178670949571

c66

c66

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1129.8288486740757, 108.95694727112623

c67

c67

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1060.145770236779, 100.0

c68

c68

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
957.1787997289646, 179.0

c69

c69

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
264.0, 127.0

c7

c7

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
873.0, 236.58983729664445

c70

c70

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
929.2907169448572, 230.0

c71

c71

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
741.9294846883888, 529.0

c72

c72

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
643.7971939837378, 544.4950454179639

c73

c73

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
532.38278102646, 423.0

c74

c74

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
344.0, 564.7241905236059

c75

c75

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
344.0, 701.8858234993185

c76

c76

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
568.0, 543.7984506178286

c77

c77

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
575.2289589627687, 374.0

c78

c78

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
344.0, 637.5777087639997

c79

c79

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
209.0, 198.3711937189796

c8

c8

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
690.0542771354775, 372.0

c80

c80

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
443.0, 427.0597032600564

c81

c81

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
500.2483558864032, 430.0

c82

c82

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
814.8709592807993, 412.0

c83

c83

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
500.7272287692391, 435.0

c84

c84

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
443.0, 433.5150582239837

c85

c85

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
283.0, 204.0

c9

c9

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
826.9336200532975, 915.0284322291311

c94

c94

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
388.1554175279993, 915.0

c95

c95

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
368.0, 553.0

c96

c96

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
313.0, 612.0

c97

c97

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
422.6564023547028, 624.4376015698018

c98

c98

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
344.9691115068547, 624.0

c99

c99

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back