1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/15075353.csml convertedTime:2009.07.01.10:45

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Post-transcriptional regulation of proinflammatory proteins.
Authors Anderson P, Phillips K, Stoecklin G, Kedersha N.
Affiliation Immunology and Allergy, Brigham and Women's Hospital, Smith 652, One Jimmy FundWay, Boston, MA 02115, USA. panderson@rics.bwh.harvard.edu
Abstract Post-transcriptional mechanisms play a critical role in regulating theexpression of numerous proteins that promote inflammatory arthritis. The mRNAsencoding a subset of these proteins possess adenine/uridine-rich elements (AREs)in their 3'-untranslated regions that profoundly influence the rate at whichmRNA is degraded and translated into protein. Tristetraprolin (TTP) and T cellintracellular antigen-1 (TIA-1) are ARE-binding proteins that dampen theexpression of this class of proteins by promoting mRNA degradation and proteintranslation, respectively. We have discovered that TIA-1 and TTP function asarthritis-suppressor genes: TIA-1-/- mice develop mild arthritis, TTP-/- micedevelop severe arthritis, and TIA-1-/-TTP-/- mice develop very severe arthritis.Paradoxically, lipopolysaccharide (LPS)-activated macrophages derived fromTIA-1-/-TTP-/- macrophages produce less tumor necrosis factor alpha (TNF-alpha)than TIA-1-/- or TTP-/- macrophages. The bone marrows of these mice exhibitincreased cellularity, reflecting the presence of mature neutrophils thatsecrete TNF-alpha in response to LPS stimulation. We hypothesize thatTIA-1-/-TTP-/- neutrophils are a source of arthritigenic TNF-alpha, whichpromotes severe erosive arthritis in these mice.
PMID 15075353
Model Abstract

Entity

G010329:TNF-alpha G029941:COX2 MO000000022:p38 MO000000074:14-3-3 MO000000289:TNF-alpha MO000000310:arachidonic acid MO000008179:PKR MO000016882:LPS MO000017266:COX-2 MO000021832:prostaglandins MO000069272:TIA1 e1: e10: e11:TTP e12:TTP e13:TLRs e14:LPS:TLRs e15:PKR{active} e16:PERK e17:PERK e18:GCN2 e19:GCN2{active} e2: e20:eIF2alpha e21:eIF2alpha{p} e22:TTP e23:TTP{p} e24:alkaline phosphatase e25:MK2 e26:TTP{p}:14-3-3 e27:TNF-alpha:TNFR e28:TNFR e29:p38 inhibitor e3: e30:intiation complex e31:mRNA e32:initiation complex:TIA1:mRNA e4: e5:MMP13 e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:NTPs e60: e61: e62: e7: e8: e9:

Process

p1 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p2 p20 p21 p22 p3 p4 p5 p6 p7 p8 p9
Model Detail
492.0, 1076.0
32.0, 32.0

TNF-alpha

--

G010329

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p8

p3 p7

true true true true

csml-variable:Double

m93309

10

false

infinite

0

unit false false false
TRANSFACG010329

--

Go back
688.0, 1156.0
40.0, 40.0

COX2

--

G029941

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p21

--

true true true true

csml-variable:Double

m108639

10

false

infinite

0

unit false false false
TRANSFACG029941

--

Go back
872.0, 488.0
40.0, 40.0

p38

--

MO000000022

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p17

true true true true

csml-variable:Double

m25

10

false

infinite

0

unit false false false
TRANSPATHMO000000022

--

Go back
789.0, 613.0
30.0, 30.0

14-3-3

--

MO000000074

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p19

true true true true

csml-variable:Double

m66

10

false

infinite

0

unit false false false
TRANSPATHMO000000074

--

Go back
1194.0, 902.0
36.0, 36.0

TNF-alpha

--

MO000000289

cso30:c:Protein

cso30:i:CC_CellComponent

--

p7

p20

true true true true

csml-variable:Double

m230

10

false

infinite

0

unit false false false
InterProIPR003636
TRANSPATHMO000000289

--

Go back
405.0, 449.0
29.0, 29.0

arachidonic acid

--

MO000000310

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1

true true true true

csml-variable:Double

m349736

10

false

infinite

0

unit false false false
TRANSPATHMO000000310

--

Go back
251.0, 535.0
33.0, 33.0

PKR

--

MO000008179

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p9

true true true true

csml-variable:Double

m1055

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000008179

--

Go back
1190.0, 670.0
36.0, 36.0

LPS

--

MO000016882

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p5

true true true true

csml-variable:Double

m155666

10

false

infinite

0

unit false false false
TRANSPATHMO000016882

--

Go back
535.0, 567.0
34.0, 34.0

COX-2

--

MO000017266

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p1

true true true true

csml-variable:Double

m2122

10

false

infinite

0

unit false false false
InterProIPR002016
TRANSPATHMO000017266

--

Go back
668.0, 448.0
32.0, 32.0

prostaglandins

--

MO000021832

cso30:c:Protein

cso30:i:CC_CellComponent

--

p1

--

true true true true

csml-variable:Double

m6166

10

false

infinite

0

unit false false false
EnsemblENSG00000035862
TRANSPATHMO000021832

--

Go back
399.0, 1103.0
33.0, 33.0

TIA1

--

MO000069272

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p22

true true true true

csml-variable:Double

m44116

10

false

infinite

0

unit false false false
TRANSPATHMO000069272

--

Go back
76.82921726248895, 148.36241342287627
990.4056548041356, 1197.7987975084177

--

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
86.37170678684701, 166.67021340868712
960.0063679435196, 1124.8265409940095

--

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
561.0, 1154.06
37.919999999999995, 28.43999999999999

TTP

--

e11

cso30:c:Protein

cso30:i:CC_Nucleoplasm

--

p6

p3

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
449.0, 1019.5017301038062
45.93425605536332, 24.498269896193772

TTP

--

e12

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p4

p6

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
1008.5, 574.0
39.0, 60.0

TLRs

--

e13

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p5

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
1016.5, 706.0
31.0, 60.0

LPS:TLRs

--

e14

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p5

p4 p6 p7 p8

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
255.0, 687.0
33.0, 33.0

PKR{active}

--

e15

cso30:c:Protein

cso30:i:CC_CellComponent

--

p9

p12

true true true true

csml-variable:Double

m15

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000008179

--

Go back
385.0, 535.4677268475209
21.463985032740876, 49.53227315247894

PERK

--

e16

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p10

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
386.0, 696.7408793264734
20.478952291861553, 47.25912067352666

PERK

--

e17

cso30:c:Protein

cso30:i:CC_Cytosol

--

p10

p13

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
684.0, 545.407828536929
47.176494264439526, 29.092171463071043

GCN2

--

e18

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p11

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
684.0, 689.5120748641579
47.00744616623063, 28.98792513584222

GCN2{active}

--

e19

cso30:c:Protein

cso30:i:CC_Cytosol

--

p11

p14

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
76.82921726248895, 148.36241342287627
990.4056548041356, 1197.7987975084177

--

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
347.0, 785.0005031193399
49.45864359025961, 30.499496880660093

eIF2alpha

--

e20

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p12 p13 p14

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
607.0, 783.7317073170732
41.58536585365853, 33.26829268292683

eIF2alpha{p}

--

e21

cso30:c:Protein

cso30:i:CC_Cytosol

--

p12 p13 p14

p15

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
901.0, 1226.06
37.919999999999995, 28.43999999999999

TTP

--

e22

cso30:c:Protein

cso30:i:CC_Nucleoplasm

--

p16

p17 p18

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
921.0, 1037.8292682926826
46.46341463414634, 37.170731707317074

TTP{p}

--

e23

cso30:c:Protein

cso30:i:CC_Cytosol

--

p17 p18

p16 p19

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
829.5, 1229.5139867176495
28.049708190782855, 45.486013282350584

alkaline phosphatase

--

e24

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p16

true true true true

csml-variable:Double

m24

0

false

infinite

0

unit false false false

--

Go back
864.0, 713.407828536929
47.176494264439526, 29.092171463071043

MK2

--

e25

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p18

true true true true

csml-variable:Double

m26

0

false

infinite

0

unit false false false

--

Go back
928.5, 580.816530578237
31.999833361106482, 39.183469421763036

TTP{p}:14-3-3

--

e26

cso30:c:Complex

cso30:i:CC_Cytosol

--

p19

--

true true true true

csml-variable:Double

m27

0

false

infinite

0

unit false false false

--

Go back
1016.5, 862.0
31.0, 60.0

TNF-alpha:TNFR

--

e27

cso30:c:Complex

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

p20

p2

true true true true

csml-variable:Double

m28

0

false

infinite

0

unit false false false

--

Go back
1004.5, 990.0
39.0, 60.0

TNFR

--

e28

cso30:c:Protein

cso30:i:CC_PlasmaMembrane_IntegralToPlasmaMembrane_

--

--

p20

true true true true

csml-variable:Double

m29

0

false

infinite

0

unit false false false

--

Go back
282.0, 851.0
60.0, 34.0

p38 inhibitor

--

e29

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p2 p8 p21

true true true true

csml-variable:Double

m30

0

false

infinite

0

unit false false false

--

Go back
96.63733035857162, 164.86101944916305
950.7894286119699, 1164.8015854558453

--

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
350.5, 1118.0
43.0, 60.0

intiation complex

--

e30

cso30:c:Complex

cso30:i:CC_Cytosol

--

--

p22

true true true true

csml-variable:Double

m31

0

false

infinite

0

unit false false false

--

Go back
437.0, 1201.5432525951555
53.35640138408304, 28.456747404844293

mRNA

--

e31

cso30:c:mRNA

cso30:i:CC_Cytosol

--

--

p22

true true true true

csml-variable:Double

m32

0

false

infinite

0

unit false false false

--

Go back
518.0, 1174.0
36.0, 60.0

initiation complex:TIA1:mRNA

--

e32

cso30:c:Complex

cso30:i:CC_Cytosol

--

p22

--

true true true true

csml-variable:Double

m33

0

false

infinite

0

unit false false false

--

Go back
133.28233958632484, 193.73357999516475
877.4994101564643, 1107.0564643638404

--

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
642.0, 988.0
60.0, 32.0

MMP13

--

e5

cso30:c:mRNA

cso30:i:CC_Cytosol

--

p2

--

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
286.474820449144, 839.1315368726387
538.6013241569034, 406.84242790105947

--

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
344.6477753860161, 848.773110958035
314.93634224444645, 394.3113469595483

--

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
293.4956943208354, 844.5616719472935
524.5595764135209, 395.9821577517497

--

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
294.49867630250566, 845.3970773433941
522.5536124501801, 394.3113469595483

--

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
286.474820449144, 839.1315368726387
538.6013241569034, 406.84242790105947

--

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
286.474820449144, 839.1315368726387
538.6013241569034, 406.84242790105947

--

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
294.49867630250566, 845.3970773433941
522.5536124501801, 394.3113469595483

--

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
679.6437572638666, 1006.2126160927861
33.64885138615356, 25.371680574324557

--

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
591.3813428768881, 1123.1693715468891
95.28328825867004, 71.8448640646635

--

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
286.474820449144, 839.1315368726387
538.6013241569034, 406.84242790105947

--

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
645.0, 1079.6497120921304
45.18234165067179, 24.850287907869482

NTPs

--

e6

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

p3

--

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
413.42012205186904, 1019.9289500652118
17.056712544534104, 6.8403616518535335

--

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
412.85055013959044, 999.52937292398
58.38112100853964, 87.52841819900742

--

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
437.34214236756367, 1056.4584254111392
9.113150596454958, 7.590540331621236

--

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
89.84170297752273, 153.18245047388007
971.2793877977546, 1146.3315643758408

--

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
93.3116991681984, 173.41409487609064
931.759890256536, 1126.8724796776016

--

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
102.5650223433335, 193.64573927830125
927.5058952551688, 1112.0938294753241

--

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
538.0, 450.0
27.0, 27.0

p1

p1

cso30:i:ME_UnknownProduction

cso30:i:CC_Cytosol

--

MO000000310 MO000017266

MO000021832

true true true true

--

and

mass

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

m349736*m2122*0.1

nodelay

--

true

0

false

PMID: 15075353, 12086290, 11177775 COX-2 is an enzyme that converts arachidonic acid into proinflammatory prostaglandins.

Go back
384.0, 624.0
23.0, 23.0

p10

p10

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e16

e17

true true true true

--

and

mass

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

m16*0.1

nodelay

--

true

0

false

PMID: 15075353, 10557102, 10655230, 10882126, 11106749 Stress-induced translational arrest is characterized by the activation of one or more members of a family of serine/threonine kinases [e.g., double-stranded RNA-dependent protein kinase R (PKR), PKR-like endoplasmic reticulum kinase (PERK), GCN2.

Go back
696.0, 628.0
23.0, 23.0

p11

p11

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

e18

e19

true true true true

--

and

mass

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

m18*0.1

nodelay

--

true

0

false

PMID: 15075353, 10557102, 10655230, 10882126, 11106749 Stress-induced translational arrest is characterized by the activation of one or more members of a family of serine/threonine kinases [e.g., double-stranded RNA-dependent protein kinase R (PKR), PKR-like endoplasmic reticulum kinase (PERK), GCN2.

Go back
495.0, 787.0
26.0, 26.0

p12

p12

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e20 e15

e21

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c28 : 1
stoichiometry:c30 : 1
stoichiometry:c29 : 1

m20*m15*0.1

nodelay

--

true

0

false

PMID: 15075353, 11909525 These kinases phosphorylate eukaryotic initiation factor 2{alpha} (eIF2{alpha}), a component of the ternary complex that loads tRNAiMet onto the small ribosomal subunit to initiate protein synthesis

Go back
548.0, 748.0
23.0, 23.0

p13

p13

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e20 e17

e21

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c31 : 1
stoichiometry:c33 : 1
stoichiometry:c32 : 1

m20*m17*0.1

nodelay

--

true

0

false

PMID: 15075353, 11909525 These kinases phosphorylate eukaryotic initiation factor 2{alpha} (eIF2{alpha}), a component of the ternary complex that loads tRNAiMet onto the small ribosomal subunit to initiate protein synthesis

Go back
436.0, 828.0
23.0, 23.0

p14

p14

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e20 e19

e21

true true true true

--

and

mass

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

m20*m19*0.1

nodelay

--

true

0

false

PMID: 15075353, 11909525 These kinases phosphorylate eukaryotic initiation factor 2{alpha} (eIF2{alpha}), a component of the ternary complex that loads tRNAiMet onto the small ribosomal subunit to initiate protein synthesis

Go back
758.0, 786.0
27.0, 27.0

p15

p15

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e21

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c37 : 1

1.0*0.1

nodelay

--

true

0

false

PMID: 15075353, 11438658 Phosphorylation of eIF2{alpha} inhibits protein translation by reducing the availability of an active ternary complex.

Go back
908.0, 1152.0
23.0, 23.0

p16

p16

cso30:i:ME_Dephosphorylation

cso30:i:CC_Cytosol

--

e23 e24

e22

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c38 : 1
stoichiometry:c40 : 1
stoichiometry:c39 : 1

m23*m24*0.1

nodelay

--

true

0

false

PMID: 15075353, 11546803 In extracts of 293 cells, calf intestinal alkaline phosphatase-induced dephosphorylation of recombinant TTP increases its affinity for AREs.

Go back
967.0, 1163.0
25.0, 25.0

p17

p17

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e22 MO000000022

e23

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c41 : 1
stoichiometry:c43 : 1
stoichiometry:c42 : 1

m22*m25*0.1

nodelay

--

true

0

false

PMID: 15075353, 11546803, 11533235 One of the candidate substrates for p38MAPK is TTP.

Go back
871.0, 1115.0
25.0, 25.0

p18

p18

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

e22 e25

e23

true true true true

--

and

mass

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

m22*m26*0.1

nodelay

--

true

0

false

PMID: 15075353 We found that MK2-induced phosphorylation of TTP results in the assembly of 14-3-3:TTP complexes, which are actively excluded from SGs.

Go back
930.0, 842.0
27.0, 27.0

p19

p19

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

MO000000074 e23

e26

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c47 : 1
stoichiometry:c48 : 1
stoichiometry:c49 : 1

m66*m23*0.1

nodelay

--

true

0

false

PMID: 15075353 We identified serine residues 52 and 178 as sites that are phosphorylated following p38MAPK/MK2 activation to create 14-3-3-binding sites.

Go back
660.0, 912.0
23.0, 23.0

p2

p2

cso30:i:ME_GeneExpression

cso30:i:CC_Cytosol

--

e27 e29

e5

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c5 : 1
stoichiometry:c55 : 1
stoichiometry:c4 : 1

m28*0.1

nodelay

--

true

0

false

PMID: 15075353, 12010565, 11817610, 11040455, 10517187 MMP-13 is a TNF-{alpha}-induced collagenase that has been implicated in proinflammatory, angiogenic, and destructive processes within the joint of patients with rheumatoid arthritis. PMID: 15075353, 12767518, 12060661, 14516792, 12937622, 12852754, 12874238 pharmacological inhibitors of p38MAPK prevent the expression of TNF-{alpha}, COX-2, MMP-13, and other proinflammatory proteins.

Go back
1137.0, 981.0
21.0, 21.0

p20

p20

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e28 MO000000289

e27

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c50 : 1
stoichiometry:c51 : 1
stoichiometry:c52 : 1

m29*m230*0.1

nodelay

--

true

0

false

PMID: 15075353, 12010565, 11817610, 11040455, 10517187 MMP-13 is a TNF-{alpha}-induced collagenase that has been implicated in proinflammatory, angiogenic, and destructive processes within the joint of patients with rheumatoid arthritis.

Go back
763.0, 1091.0
25.0, 25.0

p21

p21

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e29

G029941

true true true true

--

and

mass

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

1.0*0.1

nodelay

--

true

0

false

PMID: 15075353, 12767518, 12060661, 14516792, 12937622, 12852754, 12874238 pharmacological inhibitors of p38MAPK prevent the expression of TNF-{alpha}, COX-2, MMP-13, and other proinflammatory proteins.

Go back
455.0, 1131.0
25.0, 25.0

p22

p22

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

e30 MO000069272 e31

e32

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c57 : 1
stoichiometry:c58 : 1
stoichiometry:c59 : 1
stoichiometry:c60 : 1

m31*m44116*m32*0.1

nodelay

--

true

0

false

PMID: 15075353 TIA-1 interacts with specific components of the initiation complex that are assembled at the 5'-end of the transcript.

Go back
572.0, 1079.5
24.5, 24.5

p3

p3

cso30:i:ME_UnknownDegradation

cso30:i:CC_Nucleoplasm

--

G010329 e11

e6

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c6 : 1
stoichiometry:c8 : 1
stoichiometry:c7 : 1

m93309*m11*0.1

nodelay

--

true

0

false

PMID: 15075353, 10330172, 10751406, 11279239, 9703499 TTP is a zinc-finger protein that promotes the degradation of TNF-{alpha} transcripts.

Go back
459.0, 927.0
25.0, 25.0

p4

p4

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e14

e12

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c13 : 1
stoichiometry:c9 : 1

m14*0.1

nodelay

--

true

0

false

PMID: 15075353, 9703499 In macrophages, its induction by lipopolysaccharide (LPS) appears to prevent the pathological overexpression of this proinflammatory cytokine.

Go back
1126.0, 678.0
19.0, 19.0

p5

p5

cso30:i:ME_Binding

cso30:i:CC_Extracellular

--

e13 MO000016882

e14

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c10 : 1
stoichiometry:c11 : 1
stoichiometry:c12 : 1

m13*m155666*0.1

nodelay

--

true

0

false

PMID: 15075353, 9703499 In macrophages, its induction by lipopolysaccharide (LPS) appears to prevent the pathological overexpression of this proinflammatory cytokine.

Go back
248.0, 1024.0
24.0, 24.0

p6

p6

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

e12 e14

e11

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c14 : 1
stoichiometry:c16 : 1
stoichiometry:c15 : 1

m12*m14*0.1

nodelay

--

true

0

false

PMID: 15075353, 9703499 In macrophages, its induction by lipopolysaccharide (LPS) appears to prevent the pathological overexpression of this proinflammatory cytokine.

Go back
897.0, 1009.0
21.0, 21.0

p7

p7

cso30:i:ME_Translation

cso30:i:CC_Extracellular

--

G010329 e14

MO000000289

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c18 : 1
stoichiometry:c19 : 1
stoichiometry:c17 : 1

m93309*m14*0.1

nodelay

--

true

0

false

PMID: 15075353, 10921895, 11762949 LPS-activated macrophages derived from wild-type and TIA-1?/? mice express similar amounts of TNF-{alpha} transcripts, macrophages lacking TIA-1 produce significantly more TNF-{alpha} protein than wild-type controls.

Go back
551.0, 1019.0
25.0, 25.0

p8

p8

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e14 e29

G010329

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c21 : 1
stoichiometry:c56 : 1
stoichiometry:c20 : 1

m14*0.1

nodelay

--

true

0

false

PMID: 15075353, 10921895, 11762949 LPS-activated macrophages derived from wild-type and TIA-1?/? mice express similar amounts of TNF-{alpha} transcripts, macrophages lacking TIA-1 produce significantly more TNF-{alpha} protein than wild-type controls. PMID: 15075353, 12767518, 12060661, 14516792, 12937622, 12852754, 12874238 pharmacological inhibitors of p38MAPK prevent the expression of TNF-{alpha}, COX-2, MMP-13, and other proinflammatory proteins.

Go back
259.0, 611.5
24.5, 24.5

p9

p9

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

MO000008179

e15

true true true true

--

and

mass

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

m1055*0.1

nodelay

--

true

0

false

PMID: 15075353, 10557102, 10655230, 10882126, 11106749 Stress-induced translational arrest is characterized by the activation of one or more members of a family of serine/threonine kinases [e.g., double-stranded RNA-dependent protein kinase R (PKR), PKR-like endoplasmic reticulum kinase (PERK), GCN2.

Go back
565.0, 464.0

c1

c1

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1048.0, 619.0

c10

c10

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1153.0, 688.0

c11

c11

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1055.2636750760037, 693.0

c12

c12

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
491.5175234454968, 742.0

c13

c13

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
279.99795794642665, 1032.0

c14

c14

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
272.0, 1041.0

c15

c15

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
279.45847718143517, 742.0

c16

c16

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
918.0, 928.5050335913174

c17

c17

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
524.0, 1023.4143612604037

c18

c18

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
916.1986338408371, 766.0

c19

c19

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
434.0, 464.0

c2

c2

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
528.4715290310506, 1044.0

c20

c20

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
582.7675553177322, 746.0

c21

c21

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
269.0, 568.0

c22

c22

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
271.0, 636.0

c23

c23

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
396.0, 585.0

c24

c24

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
396.0, 647.0

c25

c25

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
708.0, 575.0

c26

c26

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
708.0, 651.0

c27

c27

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
396.0, 800.0

c28

c28

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
521.0, 800.0

c29

c29

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
552.0, 485.0

c3

c3

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
288.0, 711.0

c30

c30

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
396.0, 764.6480838483988

c31

c31

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
571.0, 766.0

c32

c32

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
406.0, 723.0

c33

c33

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
396.0, 813.0

c34

c34

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
459.0, 806.7410294091843

c35

c35

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
466.09773440987675, 717.0

c36

c36

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
649.0, 800.0

c37

c37

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
924.7246999450019, 1075.0

c38

c38

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
920.0, 1175.0

c39

c39

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
672.0, 935.0

c4

c4

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
858.0, 1181.0389749949209

c40

c40

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
933.0, 1193.8076214712466

c41

c41

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
952.2667691281392, 1082.6721416644712

c42

c42

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
895.0, 528.0

c43

c43

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
890.4766883796864, 1147.6069714518937

c44

c44

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
895.0, 1081.1709862283205

c45

c45

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
884.0860165328912, 743.0

c46

c46

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
813.0, 643.0

c47

c47

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
944.0, 877.0

c48

c48

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
944.0, 628.0

c49

c49

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
690.9679231718661, 893.0

c5

c5

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1044.0, 996.7620869714772

c50

c50

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1163.2975823717736, 938.0

c51

c51

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1054.049996270548, 910.234266436317

c52

c52

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
732.5099956953176, 1116.0

c53

c53

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
342.0, 883.0

c54

c54

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
342.0, 873.0

c55

c55

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
338.0, 885.0

c56

c56

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
394.0, 1145.2621542145662

c57

c57

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
432.0, 1127.0

c58

c58

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
465.0, 1163.9924492668404

c59

c59

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
524.0, 1092.0

c6

c6

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
480.0, 1155.0

c60

c60

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
597.0, 1092.0

c7

c7

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
581.0, 1111.9936076697743

c8

c8

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
472.0, 952.0

c9

c9

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back