1. Information
    majorVersion:3 minorVersion:0 projectID:local projectVersionID:undef fileName:/home/ikeda/eclipse/workspace/macrophage/csml/ok/csml/18922786.csml convertedTime:2009.07.01.11:22

  2. Original Literature
  3. Model OverView
  4. Model Abstracts
  5. Model Detail
  6. Download
Original Literature Model OverView
Publication
Title Acetylation of MKP-1 and the control of inflammation.
Authors Chi H, Flavell RA.
Affiliation Department of Immunology, St. Jude Children's Research Hospital, Memphis, TN38105, USA. hongbo.chi@stjude.org
Abstract Innate immune responses mediated by Toll-like receptors (TLRs), a class ofpattern-recognition receptors, play a critical role in the defense againstmicrobial pathogens. However, excessive TLR-mediated responses result in sepsis,autoimmunity, and chronic inflammation. To prevent deleterious activation ofTLRs, cells have evolved multiple mechanisms that inhibit innate immunereactions. Stimulation of TLRs induces the expression of the gene encoding themitogen-activated protein kinase (MAPK) phosphatase-1 (MKP-1), anuclear-localized dual-specificity phosphatase that preferentiallydephosphorylates p38 MAPK and c-Jun N-terminal kinase (JNK), resulting in theattenuation of TLR-triggered production of proinflammatory cytokines. MKP-1 isposttranslationally modified by multiple mechanisms, including phosphorylation.A study now demonstrates that MKP-1 is also acetylated on a key lysine residuefollowing stimulation of TLRs. Acetylation of MKP-1 promotes the interaction ofMKP-1 with its substrate p38 MAPK, which results in dephosphorylation of p38MAPK and the inhibition of innate immunity.
PMID 18922786
Model Abstract

Entity

G010262:IL-6 G010329:TNF-alpha MO000000011:ERK MO000000015:Raf-1 MO000000022:p38 MO000000023:JNK MO000000038:Elk-1 MO000000058:NF-kappaB MO000000276:AP-1 MO000000289:TNF-alpha MO000016573:MyD88 MO000016645:PKCepsilon MO000016665:IFNgamma MO000016808:TGFbeta MO000016814:MKP-1 MO000017247:IL-10 MO000019984:p300 MO000021732:glucocorticoids MO000041125:TRIF e1: e10: e11:differentiation genes e12:apoptosis e13:proinflammatory cytokines e14:MAP3K e15:MAP2K{p} e16:MAP2K e17:MAPK e18:MAPK{p} e19:AP-1{p} e2: e20:TLR e21:MKP-1 e22:TLR:MyD88 e23:TLR:TRIF e24:Raf-1{active} e25:PKCepsilon{active} e26:ERK{active} e27:p38{active} e28:JNK{active} e29:MKP-1{p} e3: e30:SCF ubiquitin liagse e31:MKP-1{p}:SCF ubiquitin liagse e32:degradants e33:ROS e34:NOS2 e35:Elk-1{p} e36:MKP-1:p300 e37:MKP-1{Ac} e38:p38{p} e39:MKP-1{Ac}:p38{p} e4: e40:MKP-1{Ac}:p38 e41:MKP-1{inactive} e5:HDAC inhibitors e50: e51: e52: e53: e54: e55: e56: e57: e58: e59: e6:cell growth arrest genes e60: e61: e62: e7: e8: e9:

Process

p1 p10 p11 p12 p13 p14 p15 p16 p17 p18 p19 p2 p20 p21 p22 p23 p24 p25 p26 p27 p28 p29 p3 p30 p31 p32 p33 p34 p35 p36 p37 p38 p39 p4 p40 p5 p6 p7 p8 p9
Model Detail
848.0, 944.0
24.0, 24.0

IL-6

--

G010262

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p34

--

true true true true

csml-variable:Double

m93248

10

false

infinite

0

unit false false false
TRANSFACG010262

--

Go back
801.0, 1001.0
22.0, 22.0

TNF-alpha

--

G010329

cso30:c:mRNA

cso30:i:CC_CellComponent

--

p33

--

true true true true

csml-variable:Double

m93309

10

false

infinite

0

unit false false false
TRANSFACG010329

--

Go back
392.0, 484.0
24.0, 24.0

ERK

--

MO000000011

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p16

true true true true

csml-variable:Double

m27

10

false

infinite

0

unit false false false
TRANSPATHMO000000011

--

Go back
547.0, 427.0
18.0, 18.0

Raf-1

--

MO000000015

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p13

true true true true

csml-variable:Double

m24

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000000015

--

Go back
524.0, 600.0
15.0, 15.0

p38

--

MO000000022

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p19 p39

true true true true

csml-variable:Double

m29

10

false

infinite

0

unit false false false
TRANSPATHMO000000022

--

Go back
367.0, 587.0
18.0, 18.0

JNK

--

MO000000023

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p20 p28 p29

true true true true

csml-variable:Double

m30

10

false

infinite

0

unit false false false
TRANSPATHMO000000023

--

Go back
847.0, 655.0
18.0, 18.0

Elk-1

--

MO000000038

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p35

true true true true

csml-variable:Double

m40

10

false

infinite

0

unit false false false
InterProIPR002341
TRANSPATHMO000000038

--

Go back
497.0, 377.0
22.0, 22.0

NF-kappaB

--

MO000000058

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p28

true true true true

csml-variable:Double

m37

10

false

infinite

0

unit false false false
TRANSPATHMO000000058

--

Go back
1102.0, 1010.0
20.0, 20.0

AP-1

--

MO000000276

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p7

true true true true

csml-variable:Double

m219

10

false

infinite

0

unit false false false
TRANSPATHMO000000276

--

Go back
151.0, 411.0
21.0, 21.0

TNF-alpha

--

MO000000289

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p28 p29

true true true true

csml-variable:Double

m230

10

false

infinite

0

unit false false false
InterProIPR003636
TRANSPATHMO000000289

--

Go back
293.0, 825.0
22.0, 22.0

MyD88

--

MO000016573

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p10

true true true true

csml-variable:Double

m1572

10

false

infinite

0

unit false false false
InterProIPR000157
TRANSPATHMO000016573

--

Go back
597.0, 469.0
22.0, 22.0

PKCepsilon

--

MO000016645

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p14

true true true true

csml-variable:Double

m1629

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000016645

--

Go back
170.0, 890.0
20.0, 20.0

IFNgamma

--

MO000016665

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m1639

10

false

infinite

0

unit false false false
InterProIPR002069
TRANSPATHMO000016665

--

Go back
163.0, 967.0
18.0, 18.0

TGFbeta

--

MO000016808

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p23

true true true true

csml-variable:Double

m1746

10

false

infinite

0

unit false false false
TRANSPATHMO000016808

--

Go back
558.0, 538.0
20.0, 20.0

MKP-1

--

MO000016814

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m1752

10

false

infinite

0

unit false false false
InterProIPR000340
TRANSPATHMO000016814

--

Go back
163.0, 1027.0
18.0, 18.0

IL-10

--

MO000017247

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p24

true true true true

csml-variable:Double

m2103

10

false

infinite

0

unit false false false
InterProIPR000098
TRANSPATHMO000017247

--

Go back
1046.0, 602.0
20.0, 20.0

p300

--

MO000019984

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m4512

10

false

infinite

0

unit false false false
InterProIPR000433
TRANSPATHMO000019984

--

Go back
757.0, 565.0
22.0, 22.0

glucocorticoids

--

MO000021732

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p22 p27

true true true true

csml-variable:Double

m6069

10

false

infinite

0

unit false false false
TRANSPATHMO000021732

--

Go back
313.0, 557.0
21.0, 21.0

TRIF

--

MO000041125

cso30:c:Protein

cso30:i:CC_CellComponent

--

--

p11

true true true true

csml-variable:Double

m18998

10

false

infinite

0

unit false false false
TRANSPATHMO000041125

--

Go back
208.61101843926383, 157.57413371771582
1050.8217652382598, 1525.793203125952

--

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
212.56356094620713, 204.38080497596414
999.7401320018845, 1406.3532542275818

--

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
652.0, 1077.0
55.7439446366782, 29.730103806228374

differentiation genes

--

e11

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p2

--

true true true true

csml-variable:Double

m11

0

false

infinite

0

unit false false false

--

Go back
498.0, 1142.0
52.57785467128028, 28.041522491349482

apoptosis

--

e12

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p3

--

true true true true

csml-variable:Double

m12

0

false

infinite

0

unit false false false

--

Go back
707.0, 1011.0
50.55363321799308, 26.961937716262977

proinflammatory cytokines

--

e13

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p4

--

true true true true

csml-variable:Double

m13

0

false

infinite

0

unit false false false

--

Go back
1032.0, 767.5
23.839999999999993, 17.879999999999995

MAP3K

--

e14

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p5

true true true true

csml-variable:Double

m14

0

false

infinite

0

unit false false false

--

Go back
959.0, 829.0
26.585365853658534, 21.268292682926827

MAP2K{p}

--

e15

cso30:c:Protein

cso30:i:CC_Cytosol

--

p5

p6

true true true true

csml-variable:Double

m15

0

false

infinite

0

unit false false false

--

Go back
1110.0, 831.5
27.422016502314346, 16.910243509760516

MAP2K

--

e16

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p5

true true true true

csml-variable:Double

m16

0

false

infinite

0

unit false false false

--

Go back
1048.5, 896.0
14.408331656268864, 23.36486214530086

MAPK

--

e17

cso30:c:Protein

cso30:i:CC_Cytosol

--

--

p6

true true true true

csml-variable:Double

m17

0

false

infinite

0

unit false false false

--

Go back
961.0, 960.0
29.63414634146341, 23.707317073170735

MAPK{p}

--

e18

cso30:c:Protein

cso30:i:CC_Cytosol

--

p6

p7

true true true true

csml-variable:Double

m18

0

false

infinite

0

unit false false false

--

Go back
1041.0, 1056.0
30.853658536585368, 24.682926829268293

AP-1{p}

--

e19

cso30:c:Protein

cso30:i:CC_Cytosol

--

p7

--

true true true true

csml-variable:Double

m19

0

false

infinite

0

unit false false false

--

Go back
208.61101843926383, 157.57413371771582
1050.8217652382598, 1525.793203125952

--

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
236.5, 751.0
22.041876781407588, 42.66169699627274

TLR

--

e20

cso30:c:Complex

cso30:i:CC_Cytosol

--

--

p10 p11

true true true true

csml-variable:Double

m20

0

false

infinite

0

unit false false false

--

Go back
593.0, 892.0
46.03806228373702, 24.55363321799308

MKP-1

--

e21

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

true true true true

csml-variable:Double

m21

0

false

infinite

0

unit false false false

--

Go back
239.5, 659.0
24.68416223160213, 34.4430170673518

TLR:MyD88

--

e22

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m22

0

false

infinite

0

unit false false false

--

Go back
239.5, 579.0
24.68416223160213, 34.4430170673518

TLR:TRIF

--

e23

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m23

0

false

infinite

0

unit false false false

--

Go back
643.0, 379.0
18.0, 18.0

Raf-1{active}

--

e24

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m25

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000000015

--

Go back
629.0, 581.0
22.0, 22.0

PKCepsilon{active}

--

e25

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m26

10

false

infinite

0

unit false false false
InterProIPR000719
TRANSPATHMO000016645

--

Go back
480.0, 516.0
24.0, 24.0

ERK{active}

--

e26

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m28

10

false

infinite

0

unit false false false
TRANSPATHMO000000011

--

Go back
448.0, 680.0
15.0, 15.0

p38{active}

--

e27

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m31

10

false

infinite

0

unit false false false
TRANSPATHMO000000022

--

Go back
383.0, 743.0
18.0, 18.0

JNK{active}

--

e28

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m32

10

false

infinite

0

unit false false false
TRANSPATHMO000000023

--

Go back
634.0, 522.0
20.0, 20.0

MKP-1{p}

--

e29

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m33

10

false

infinite

0

unit false false false
InterProIPR000340
TRANSPATHMO000016814

--

Go back
229.6274537440291, 178.59056902248116
1008.7888946287292, 1483.760332516424

--

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
795.0, 467.5
26.769973837794318, 16.508150533306498

SCF ubiquitin liagse

--

e30

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m34

0

false

infinite

0

unit false false false

--

Go back
880.5, 517.0
23.695717380436598, 29.01516413931012

MKP-1{p}:SCF ubiquitin liagse

--

e31

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m35

0

false

infinite

0

unit false false false

--

Go back
1070.0, 522.0
20.9707064905227, 20.271682940838613

degradants

--

e32

cso30:c:EntityBiological

cso30:i:CC_Cytosol

--

p27

--

true true true true

csml-variable:Double

m36

0

false

infinite

0

unit false false false

--

Go back
605.0, 289.0
42.89318755256518, 24.30613961312027

ROS

--

e33

cso30:c:SmallMolecule

cso30:i:CC_Cytosol

--

--

p29 p30

true true true true

csml-variable:Double

m38

0

false

infinite

0

unit false false false

--

Go back
752.0, 1073.0
40.79584775086506, 21.757785467128027

NOS2

--

e34

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p32

--

true true true true

csml-variable:Double

m39

0

false

infinite

0

unit false false false

--

Go back
875.0, 739.0
18.0, 18.0

Elk-1{p}

--

e35

cso30:c:Protein

cso30:i:CC_CellComponent

--

p35

--

true true true true

csml-variable:Double

m41

10

false

infinite

0

unit false false false
InterProIPR002341
TRANSPATHMO000000038

--

Go back
1016.5, 662.0
22.691384769205133, 27.785369105149144

MKP-1:p300

--

e36

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m42

0

false

infinite

0

unit false false false

--

Go back
1094.0, 710.0
20.0, 20.0

MKP-1{Ac}

--

e37

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m43

10

false

infinite

0

unit false false false
InterProIPR000340
TRANSPATHMO000016814

--

Go back
748.0, 672.0
15.0, 15.0

p38{p}

--

e38

cso30:c:Protein

cso30:i:CC_CellComponent

--

true true true true

csml-variable:Double

m44

10

false

infinite

0

unit false false false
TRANSPATHMO000000022

--

Go back
949.5, 779.0
20.633727712047985, 25.265789035160797

MKP-1{Ac}:p38{p}

--

e39

cso30:c:Complex

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m45

0

false

infinite

0

unit false false false

--

Go back
268.5078590578449, 215.3693308058199
931.0280840010976, 1410.202808949745

--

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
953.5, 579.0
20.633727712047985, 25.265789035160797

MKP-1{Ac}:p38

--

e40

cso30:c:Complex

cso30:i:CC_Cytosol

--

p40

--

true true true true

csml-variable:Double

m46

0

false

infinite

0

unit false false false

--

Go back
810.0, 390.0
20.0, 20.0

MKP-1{inactive}

--

e41

cso30:c:Protein

cso30:i:CC_CellComponent

--

p30

--

true true true true

csml-variable:Double

m47

10

false

infinite

0

unit false false false
InterProIPR000340
TRANSPATHMO000016814

--

Go back
771.0, 1356.5
25.876433890118733, 15.957134232239888

HDAC inhibitors

--

e5

cso30:c:Protein

cso30:i:CC_Cytosol

--

true true true true

csml-variable:Double

m5

0

false

infinite

0

unit false false false

--

Go back
318.0452924626765, 686.4972357289384
603.7469662956628, 547.5321649645964

--

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
383.25446200671445, 699.4729520520337
353.0289523591025, 530.6677245652761

--

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
325.9153646490259, 693.8051599019773
588.0068219229643, 532.9163166185185

--

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
327.03966067564727, 694.9294559285981
585.7582298697206, 530.6677245652761

--

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
318.0452924626765, 686.4972357289384
603.7469662956628, 547.5321649645964

--

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
318.0452924626765, 686.4972357289384
603.7469662956628, 547.5321649645964

--

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
327.03966067564727, 694.9294559285981
585.7582298697206, 530.6677245652761

--

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
758.7693348982443, 911.3564410532083
37.71879316398706, 34.14543381160945

--

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
659.8312845555652, 1068.757884780196
106.80812252902778, 96.68945828943593

--

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
318.0452924626765, 686.4972357289384
603.7469662956628, 547.5321649645964

--

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
550.0, 1094.0
52.83737024221453, 28.179930795847753

cell growth arrest genes

--

e6

cso30:c:mRNA

cso30:i:CC_Nucleoplasm

--

p1

--

true true true true

csml-variable:Double

m6

0

false

infinite

0

unit false false false

--

Go back
460.34505536820836, 929.8160055436804
19.119779309602436, 9.205819667586374

--

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
459.7065918169659, 902.3620728402373
65.4425140023934, 117.79652520430824

--

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
487.16052452040947, 978.9776989893808
10.215416819885787, 10.215416819885808

--

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
223.4172837234756, 162.71404618593252
1030.5287695747422, 1460.232647663104

--

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
227.09895446593208, 188.48574138312793
988.5985281972278, 1435.4450629423764

--

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
236.91674311248272, 214.25743658032337
984.0850336357139, 1416.619560631874

--

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
566.0, 1018.0
20.0, 20.0

p1

p1

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

e5

e6

true true true true

--

and

mass

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

m5*0.1

nodelay

--

true

0

false

PMID: 18922786,11902574 HDAC inhibitors induce the expression of a subset of genes involved in cell growth arrest, differentiation, and apoptosis, which accounts for the antitumor effects of these compounds

Go back
326.0, 762.0
19.0, 19.0

p10

p10

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c18 : 1
stoichiometry:c22 : 1
stoichiometry:c23 : 1

m20*m1572*0.1

nodelay

--

true

0

false

PMID: 18922786,16497588 The signals involved in TLR-induced expression of MKP-1 are beginning to be defined. Stimulation of TLRs activates two distinct pathways that are mediated by the adaptor proteins myeloid differentiation marker 88 (MyD88) and TRIF [Toll-IL-1 receptor (TIR) domain-containing adapter-inducing interferon-beta (IFN-beta)], respectively

Go back
338.0, 702.0
19.0, 19.0

p10

p11

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c25 : 1
stoichiometry:c26 : 1
stoichiometry:c27 : 1

m20*m18998*0.1

nodelay

--

true

0

false

PMID: 18922786,16497588 The signals involved in TLR-induced expression of MKP-1 are beginning to be defined. Stimulation of TLRs activates two distinct pathways that are mediated by the adaptor proteins myeloid differentiation marker 88 (MyD88) and TRIF [Toll-IL-1 receptor (TIR) domain-containing adapter-inducing interferon-beta (IFN-beta)], respectively

Go back
402.0, 890.0
19.0, 19.0

p8

p12

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c28 : 1
stoichiometry:c62 : 1
stoichiometry:c29 : 1

m23*0.1

nodelay

--

true

0

false

PMID: 18922786,16461893,16380513,12444149,15590669,16978838 In macrophages responding to TLR stimulation, there is a strong and rapid induction of MKP-1 mRNA and increase in MKP-1 protein abundance, peaking at 1 hour after stimulation PMID: 18922786,16461893 TLR-induced expression of MKP-1 is reduced in mice lacking either MyD88 or TRIF compared to that in wildtype mice, suggesting that MKP-1 is induced through both MyD88- and TRIF-dependent pathways in response to activation of TLRs PMID: 18922786,16380513 Conversely, proinflammatory stimuli such as interferon ¦Ã (IFN-gamma) attenuate MKP-1 expression to facilitate their positive effects on MAPK activation

Go back
546.0, 349.5
20.5, 20.5

p13

p13

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c31 : 1
stoichiometry:c30 : 1
stoichiometry:c32 : 1

m24*m22*0.1

nodelay

--

true

0

false

PMID: 18922786,16709817,10604989 In addition, a signaling pathway consisting of the MAP3K Raf-1 and protein kinase C epsilon (PKCepsilon) is required for TLR-induced expression of MKP-1 in macrophages

Go back
674.0, 481.5
20.5, 20.5

p13

p14

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c33 : 1
stoichiometry:c34 : 1
stoichiometry:c35 : 1

m25*m1629*0.1

nodelay

--

true

0

false

PMID: 18922786,16709817,10604989 In addition, a signaling pathway consisting of the MAP3K Raf-1 and protein kinase C epsilon (PKCepsilon) is required for TLR-induced expression of MKP-1 in macrophages

Go back
623.0, 723.0
19.0, 19.0

p15

p15

cso30:i:ME_GeneExpression

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c36 : 1
stoichiometry:c66 : 1
stoichiometry:c37 : 1

m26*0.1

nodelay

--

true

0

false

PMID: 18922786,16709817,10604989 In addition, a signaling pathway consisting of the MAP3K Raf-1 and protein kinase C epsilon (PKCepsilon) is required for TLR-induced expression of MKP-1 in macrophages PMID: 18922786,16380513 Conversely, proinflammatory stimuli such as interferon ¦Ã (IFN-¦Ã) attenuate MKP-1 expression to facilitate their positive effects on MAPK activation

Go back
453.0, 569.0
21.0, 21.0

p16

p16

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c38 : 1
stoichiometry:c39 : 1
stoichiometry:c96 : 1
stoichiometry:c40 : 1

m22*m27*0.1

nodelay

--

true

0

false

PMID: 18922786,12444149,16978838,17337450 Furthermore, ERK, JNK, and p38 MAPK have all been suggested to facilitate TLR-induced expression of MKP-1 PMID: 18922786 They found that HDAC inhibitors reduced the activation of p38 MAPK and ERK, but not JNK or the NF-KappaB pathway.

Go back
549.0, 717.0
21.0, 21.0

p17

p17

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c41 : 1
stoichiometry:c65 : 1
stoichiometry:c42 : 1

m28*0.1

nodelay

--

true

0

false

PMID: 18922786,12444149,16978838,17337450 Furthermore, ERK, JNK, and p38 MAPK have all been suggested to facilitate TLR-induced expression of MKP-1 PMID: 18922786,16380513 Conversely, proinflammatory stimuli such as interferon ¦Ã (IFN-gamma) attenuate MKP-1 expression to facilitate their positive effects on MAPK activation

Go back
478.0, 830.0
19.0, 19.0

p17

p18

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c46 : 1
stoichiometry:c64 : 1
stoichiometry:c47 : 1

m31*0.1

nodelay

--

true

0

false

PMID: 18922786,12444149,16978838,17337450 Furthermore, ERK, JNK, and p38 MAPK have all been suggested to facilitate TLR-induced expression of MKP-1 PMID: 18922786,16380513 Conversely, proinflammatory stimuli such as interferon ¦Ã (IFN-gamma) attenuate MKP-1 expression to facilitate their positive effects on MAPK activation

Go back
442.0, 614.0
19.0, 19.0

p16

p19

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c43 : 1
stoichiometry:c44 : 1
stoichiometry:c97 : 1
stoichiometry:c45 : 1

m22*m29*0.1

nodelay

--

true

0

false

PMID: 18922786,12444149,16978838,17337450 Furthermore, ERK, JNK, and p38 MAPK have all been suggested to facilitate TLR-induced expression of MKP-1 PMID: 18922786 They found that HDAC inhibitors reduced the activation of p38 MAPK and ERK, but not JNK or the NF-KappaB pathway.

Go back
614.0, 1022.0
20.0, 20.0

p1

p2

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c3 : 1
stoichiometry:c4 : 1

m5*0.1

nodelay

--

true

0

false

PMID: 18922786,11902574 HDAC inhibitors induce the expression of a subset of genes involved in cell growth arrest, differentiation, and apoptosis, which accounts for the antitumor effects of these compounds

Go back
366.0, 678.0
19.0, 19.0

p16

p20

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c48 : 1
stoichiometry:c49 : 1
stoichiometry:c50 : 1

m22*m30*0.1

nodelay

--

true

0

false

PMID: 18922786,12444149,16978838,17337450 Furthermore, ERK, JNK, and p38 MAPK have all been suggested to facilitate TLR-induced expression of MKP-1

Go back
430.0, 858.0
19.0, 19.0

p17

p21

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c51 : 1
stoichiometry:c63 : 1
stoichiometry:c52 : 1

m32*0.1

nodelay

--

true

0

false

PMID: 18922786,12444149,16978838,17337450 Furthermore, ERK, JNK, and p38 MAPK have all been suggested to facilitate TLR-induced expression of MKP-1 PMID: 18922786,16380513 Conversely, proinflammatory stimuli such as interferon ¦Ã (IFN-gamma) attenuate MKP-1 expression to facilitate their positive effects on MAPK activation

Go back
666.0, 766.0
19.0, 19.0

p22

p22

cso30:i:ME_GeneExpression

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c53 : 1
stoichiometry:c67 : 1
stoichiometry:c54 : 1

m6069*0.1

nodelay

--

true

0

false

PMID: 18922786 MKP-1 is also induced by multiple immunosuppressive agents, including glucocorticoids and anti-inflammatory cytokines, and this induction partially mediates the inhibitory effects of these agents on MAPK activation and inflammation PMID: 18922786 Figure 1A PMID: 18922786,16380513 Conversely, proinflammatory stimuli such as interferon ¦Ã (IFN-gamma) attenuate MKP-1 expression to facilitate their positive effects on MAPK activation

Go back
386.0, 966.0
19.0, 19.0

p23

p23

cso30:i:ME_GeneExpression

cso30:i:CC_NuclearChromosome

--

true true true true

--

and

mass

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

m1746*0.1

nodelay

--

true

0

false

PMID: 18922786,16184516,11842088 Induction of MKP-1 by transforming growth factor beta (TGF-beta) and IL-10 also contributes to the suppressive effects of these potent anti-inflammatory cytokines on the expression of genes encoding proinflammatory mediators. PMID: 18922786,16380513 Conversely, proinflammatory stimuli such as interferon ¦Ã (IFN-gamma) attenuate MKP-1 expression to facilitate their positive effects on MAPK activation

Go back
390.0, 1006.0
19.0, 19.0

p23

p24

cso30:i:ME_GeneExpression

cso30:i:CC_NuclearChromosome

--

true true true true

--

and

mass

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

m2103*0.1

nodelay

--

true

0

false

PMID: 18922786,16184516,11842088 Induction of MKP-1 by transforming growth factor beta (TGF-beta) and IL-10 also contributes to the suppressive effects of these potent anti-inflammatory cytokines on the expression of genes encoding proinflammatory mediators. PMID: 18922786,16380513 Conversely, proinflammatory stimuli such as interferon ¦Ã (IFN-gamma) attenuate MKP-1 expression to facilitate their positive effects on MAPK activation

Go back
486.0, 446.0
19.0, 19.0

p25

p25

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c68 : 1
stoichiometry:c69 : 1
stoichiometry:c70 : 1

m28*m1752*0.1

nodelay

--

true

0

false

PMID: 18922786 Interestingly, MKP-1 is phosphorylated by ERK in two distinct regions, which have opposing effects on its stability PMID: 1892786,10617468 Transient activation of ERK phosphorylates MKP-1 at the two extreme C-terminal Ser359 and Ser364, which enhances MKP-1 stabilization without altering its phosphatase activity

Go back
738.0, 522.0
19.0, 19.0

p26

p26

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c71 : 1
stoichiometry:c72 : 1
stoichiometry:c73 : 1

m33*m34*0.1

nodelay

--

true

0

false

PMID: 18922786,12676937,16286470 This facilitates the interaction of MKP-1 with the Skp-cullin-F-box (SCFSkp2) ubiquitin ligase, which targets MKP-1 for proteasomal degradation

Go back
982.0, 522.0
19.0, 19.0

p27

p27

cso30:i:ME_ProteasomeDegradation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c74 : 1
stoichiometry:c77 : 1
stoichiometry:c75 : 1
stoichiometry:c76 : 1

m35*0.1

nodelay

--

true

0

false

PMID: 18922786,12676937,16286470 This facilitates the interaction of MKP-1 with the Skp-cullin-F-box (SCFSkp2) ubiquitin ligase, which targets MKP-1 for proteasomal degradation PMID: 18922786 For example, glucocorticoids increase the expression of MKP-1 as well as attenuating proteasomal degradation of MKP-1.

Go back
386.0, 414.0
19.0, 19.0

p28

p28

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c78 : 1
stoichiometry:c79 : 1
stoichiometry:c80 : 1
stoichiometry:c81 : 1

m230*m37*m30*0.1

nodelay

--

true

0

false

PMID: 18922786 In the presence of the transcription factor nuclear factor-KappaB (NF-KappaB), TNF-alpha induces a rapid and transient activation of JNK.

Go back
426.0, 354.0
19.0, 19.0

p29

p29

cso30:i:ME_UnknownActivation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c82 : 1
stoichiometry:c83 : 1
stoichiometry:c84 : 1
stoichiometry:c85 : 1

m230*m38*m30*0.1

nodelay

--

true

0

false

PMID: 18922786 Reactive oxygen species (ROS) mediate sustained JNK activation in NF- KappaB?deficient cells by inactivating MKP-1 and several other MKP molecules.

Go back
514.0, 1054.0
20.0, 20.0

p1

p3

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

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

m5*0.1

nodelay

--

true

0

false

PMID: 18922786,11902574 HDAC inhibitors induce the expression of a subset of genes involved in cell growth arrest, differentiation, and apoptosis, which accounts for the antitumor effects of these compounds

Go back
702.0, 350.0
19.0, 19.0

p30

p30

cso30:i:ME_Oxidation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c86 : 1
stoichiometry:c87 : 1
stoichiometry:c88 : 1

m38*m1752*0.1

nodelay

--

true

0

false

PMID: 18922786 Reactive oxygen species (ROS) mediate sustained JNK activation in NF- KappaB?deficient cells by inactivating MKP-1 and several other MKP molecules. PMID: 18922786 This is achieved by ROS-induced oxidation of the catalytic Cys residue in the MKP molecules, resulting in the loss of phosphatase activity.

Go back
142.0, 690.0
19.0, 19.0

p31

p31

cso30:i:CE_Apoptosis_InhibitionOfCellSurvival_

cso30:i:CC_Extracellular

--

e28

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c89 : 1

m32*0.1

nodelay

--

true

0

false

PMID: 18922786,15766528 Consequently, JNK activation becomes unconstrained, eventually leading to cellular apoptosis (

Go back
755.0, 1135.0
17.0, 17.0

p32

p32

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c90 : 1
stoichiometry:c91 : 1

1.0*0.1

nodelay

--

true

0

false

PMID: 18922786 HDAC inhibitors down-regulated a subset of inflammationassociated genes, including nitric oxide synthase 2 (NOS2), TNFalpha, and IL-6.

Go back
815.0, 1095.0
17.0, 17.0

p32

p33

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c92 : 1
stoichiometry:c93 : 1

1.0*0.1

nodelay

--

true

0

false

PMID: 18922786 HDAC inhibitors down-regulated a subset of inflammationassociated genes, including nitric oxide synthase 2 (NOS2), TNFalpha, and IL-6.

Go back
855.0, 1039.0
17.0, 17.0

p32

p34

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

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

1.0*0.1

nodelay

--

true

0

false

PMID: 18922786 HDAC inhibitors down-regulated a subset of inflammationassociated genes, including nitric oxide synthase 2 (NOS2), TNFalpha, and IL-6.

Go back
806.0, 698.0
19.0, 19.0

p35

p35

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c99 : 1
stoichiometry:c111 : 1
stoichiometry:c100 : 1

m40*m44*0.1

nodelay

--

true

0

false

PMID: 18922786 In particular, HDAC inhibitors decreased phosphorylation of p38 MAPK and its downstream target Elk-1 but not the upstream MAP2Ks MKK3 or MKK6, suggesting that these inhibitors act upon the MAPK pathway at the level of p38, possibly upon a kinase or phosphatase that modifies p38 MAPK.

Go back
893.0, 621.0
17.0, 17.0

p36

p36

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c102 : 1
stoichiometry:c103 : 1
stoichiometry:c104 : 1
stoichiometry:c105 : 1

m1752*m4512*m22*0.1

nodelay

--

true

0

false

PMID: 18922786 To identify the acetylated component of the p38 MAPK pathway, Cao et al. immunoprecipitated the histone acetylase p300 and showed that it was associated with MKP-1.

Go back
1090.0, 654.0
19.0, 19.0

p37

p37

cso30:i:ME_Acetylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m42*0.1

nodelay

--

true

0

false

PMID: 18922786 Upon stimulation of TLRs, MKP-1 was acetylated at Lys57, and mutation of this residue abrogated the acetylation of MKP-1 by p300 in vitro and in TLR-stimulated cells, suggesting that Lys57 is the crucial residue required for the acetylation of MKP-1.

Go back
894.0, 702.0
19.0, 19.0

p38

p38

cso30:i:ME_Binding

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c112 : 1
stoichiometry:c109 : 1
stoichiometry:c113 : 1

m44*m43*0.1

nodelay

--

true

0

false

PMID: 18922786 Through a number of biochemical approaches, the authors demonstrated that acetylation of MKP-1 potentiated the interaction between MKP-1 and p38 and, consequently, increased the dephosphorylation of p38 by MKP-1.

Go back
686.0, 598.0
19.0, 19.0

p35

p39

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c98 : 1
stoichiometry:c101 : 1
stoichiometry:c110 : 1

m29*0.1

nodelay

--

true

0

false

PMID: 18922786 In particular, HDAC inhibitors decreased phosphorylation of p38 MAPK and its downstream target Elk-1 but not the upstream MAP2Ks MKK3 or MKK6, suggesting that these inhibitors act upon the MAPK pathway at the level of p38, possibly upon a kinase or phosphatase that modifies p38 MAPK.

Go back
662.0, 962.0
19.0, 19.0

p4

p4

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

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

1.0*0.1

nodelay

--

true

0

false

PMID: 18922786 Paradoxically, HDAC inhibitors also possess potent anti-inflammatory effects by shutting down the expression of genes encoding proinflammatory cytokines and molecules.

Go back
954.0, 678.0
19.0, 19.0

p40

p40

cso30:i:ME_Dephosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c114 : 1
stoichiometry:c115 : 1

m45*0.1

nodelay

--

true

0

false

PMID: 18922786 Through a number of biochemical approaches, the authors demonstrated that acetylation of MKP-1 potentiated the interaction between MKP-1 and p38 and, consequently, increased the dephosphorylation of p38 by MKP-1.

Go back
1034.0, 830.0
19.0, 19.0

p5

p5

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c9 : 1
stoichiometry:c10 : 1
stoichiometry:c11 : 1

m14*m16*0.1

nodelay

--

true

0

false

PMID: 18922786 Activation of MAPK is mediated by a core kinase module consisting of MAPK kinase kinase (MAPKKK, also known as MAP3K), MAPK kinase (MAPKK, also known as MAP2K), and MAPK through sequential protein phosphorylations.

Go back
966.0, 898.0
19.0, 19.0

p5

p6

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c12 : 1
stoichiometry:c13 : 1
stoichiometry:c14 : 1

m15*m17*0.1

nodelay

--

true

0

false

PMID: 18922786 Activation of MAPK is mediated by a core kinase module consisting of MAPK kinase kinase (MAPKKK, also known as MAP3K), MAPK kinase (MAPKK, also known as MAP2K), and MAPK through sequential protein phosphorylations.

Go back
1045.0, 961.0
21.0, 21.0

p7

p7

cso30:i:ME_Phosphorylation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c15 : 1
stoichiometry:c16 : 1
stoichiometry:c17 : 1

m18*m219*0.1

nodelay

--

true

0

false

PMID: 18922786,11274345,11861597 Activated MAPKs, in turn, phosphorylate activating protein 1 (AP-1) transcription factors and other targets to stimulate gene transcription and immune responses

Go back
378.0, 930.0
19.0, 19.0

p8

p8

cso30:i:ME_GeneExpression

cso30:i:CC_Nucleoplasm

--

true true true true

--

and

mass

coefficient1:0.1
coefficient2:1.0
stoichiometry:c24 : 1
stoichiometry:c61 : 1
stoichiometry:c19 : 1

m22*0.1

nodelay

--

true

0

false

PMID: 18922786,16461893,16380513,12444149,15590669,16978838 In macrophages responding to TLR stimulation, there is a strong and rapid induction of MKP-1 mRNA and increase in MKP-1 protein abundance, peaking at 1 hour after stimulation PMID: 18922786,16461893 TLR-induced expression of MKP-1 is reduced in mice lacking either MyD88 or TRIF compared to that in wildtype mice, suggesting that MKP-1 is induced through both MyD88- and TRIF-dependent pathways in response to activation of TLRs PMID: 18922786,16380513 Conversely, proinflammatory stimuli such as interferon ¦Ã (IFN-gamma) attenuate MKP-1 expression to facilitate their positive effects on MAPK activation

Go back
571.0, 619.0
17.0, 17.0

p9

p9

cso30:i:ME_Translation

cso30:i:CC_Cytosol

--

true true true true

--

and

mass

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

m21*0.1

nodelay

--

true

0

false

PMID: 18922786,16461893,16380513,12444149,15590669,16978838 In macrophages responding to TLR stimulation, there is a strong and rapid induction of MKP-1 mRNA and increase in MKP-1 protein abundance, peaking at 1 hour after stimulation PMID: 18922786,16461893 TLR-induced expression of MKP-1 is reduced in mice lacking either MyD88 or TRIF compared to that in wildtype mice, suggesting that MKP-1 is induced through both MyD88- and TRIF-dependent pathways in response to activation of TLRs

Go back
586.2034887626374, 1044.8066645445754

c1

c1

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1061.0, 840.0

c10

c10

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
825.0, 713.0

c100

c100

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
697.4617570299796, 620.9732581649403

c101

c101

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
578.0, 550.0

c102

c102

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
917.945204834583, 613.0

c103

c103

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
264.0, 631.5582542490554

c104

c104

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
910.0, 633.0

c105

c105

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1039.0, 667.2397421507617

c106

c106

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1101.0, 673.0

c107

c107

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
1069.1589675136784, 628.1143318680631

c108

c108

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
920.9921972610896, 712.353246287783

c109

c109

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
994.0, 840.0

c11

c11

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
703.0, 617.0

c110

c110

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
763.0, 683.0

c111

c111

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
763.0, 682.0

c112

c112

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
910.0, 721.0

c113

c113

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
961.0, 704.9946514126918

c114

c114

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
964.0, 612.0

c115

c115

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
973.0, 850.0

c12

c12

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
993.0, 908.0

c13

c13

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
976.0, 917.0

c14

c14

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
991.0, 972.0

c15

c15

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1072.0621504188273, 985.220185082879

c16

c16

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1056.0, 982.0

c17

c17

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
259.0, 772.0

c18

c18

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
397.0, 909.2497707842765

c19

c19

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
576.0, 1038.0

c2

c2

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
582.0227872743784, 643.9343497648748

c20

c20

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
571.1676869865141, 565.9143229085959

c21

c21

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
310.0, 788.1554175279994

c22

c22

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
269.2680368629481, 696.020613557655

c23

c23

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
261.0, 693.0

c24

c24

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
259.0, 722.1540832027904

c25

c25

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
326.0, 578.0

c26

c26

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
269.1281091079856, 617.1402359056143

c27

c27

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
261.0, 613.0

c28

c28

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
421.0, 900.0

c29

c29

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
632.4581254701067, 1049.213970351547

c3

c3

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
264.0, 375.76401768830647

c30

c30

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
556.0, 378.0

c31

c31

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
567.0, 363.0

c32

c32

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
655.0, 397.0

c33

c33

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
619.0, 482.0

c34

c34

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
648.2405150182823, 502.0

c35

c35

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
633.3995009355511, 603.0

c36

c36

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
617.796029752168, 742.0

c37

c37

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
264.0, 588.2813121968434

c38

c38

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
413.0, 508.0

c39

c39

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
633.0, 1042.0

c4

c4

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
470.0, 547.0046214722144

c40

c40

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
496.0, 540.0

c41

c41

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
563.0, 738.0

c42

c42

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
264.0, 629.0016561190512

c43

c43

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
468.8587085313798, 610.0

c44

c44

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
452.0, 633.0

c45

c45

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
457.0, 695.0

c46

c46

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
497.0, 845.0

c47

c47

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
264.0, 677.0

c48

c48

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
376.0, 605.0

c49

c49

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
538.2361888983875, 1080.0483324826273

c5

c5

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
378.0, 697.0

c50

c50

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
396.0, 761.0

c51

c51

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
449.0, 870.0

c52

c52

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
684.3318385229077, 587.0

c53

c53

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
625.3867914458883, 785.0

c54

c54

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
181.0, 976.0

c55

c55

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
405.0, 914.4690273894471

c56

c56

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
409.0, 919.6701273990304

c57

c57

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
181.0, 1017.6864540622931

c58

c58

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
190.0, 903.0

c59

c59

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
524.0, 1074.0

c6

c6

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
190.0, 905.0

c60

c60

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
190.0, 902.0

c61

c61

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
190.0, 900.0

c62

c62

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
190.0, 869.4961389383568

c63

c63

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
190.0, 842.7634786364089

c64

c64

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
190.0, 734.645258368988

c65

c65

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
190.0, 738.3788020449628

c66

c66

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
190.0, 778.9701425001454

c67

c67

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
493.0, 472.98619498539995

c68

c68

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
507.9234759599388, 471.3055042995707

c69

c69

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
676.0948296913227, 984.8472519994144

c7

c7

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
505.0, 461.0

c70

c70

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
654.0, 532.0

c71

c71

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
762.7931034482758, 484.0

c72

c72

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
757.0, 532.0

c73

c73

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
904.0, 532.0

c74

c74

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
1001.0, 532.0

c75

c75

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
829.6493265058435, 482.3426062424146

c76

c76

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
779.0, 534.7733078897743

c77

c77

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
172.0, 422.0

c78

c78

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
412.6299136967519, 392.0

c79

c79

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
681.0, 980.0

c8

c8

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
377.0, 440.9459069717681

c80

c80

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
392.1032172143252, 433.0

c81

c81

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
172.0, 367.66360695139844

c82

c82

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
452.59419940151474, 308.0

c83

c83

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
378.0, 380.7393997090084

c84

c84

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
393.90231341742196, 373.0

c85

c85

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
644.0, 313.0

c86

c86

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
576.0, 375.35913238305983

c87

c87

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
721.0, 363.0

c88

c88

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
168.81931332351894, 703.6906623402203

c89

c89

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
1044.0, 785.0

c9

c9

cso30:c:InputAssociation

--

true true true true

cso30:c:InputAssociation

threshold

--

0

1,

--

Go back
765.3498733929009, 1155.9846691969271

c90

c90

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
765.0, 1102.9114908229465

c91

c91

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
785.0, 1115.9527377529025

c92

c92

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
814.1005469701975, 1030.923938185422

c93

c93

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
786.0, 1059.8782855770817

c94

c94

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
861.3377268214706, 975.9928681081361

c95

c95

cso30:c:OutputProcess

--

true true true true

cso30:c:OutputProcess

threshold

--

0

1,

--

Go back
469.5113345780593, 593.7034939979919

c96

c96

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
457.6381047866899, 636.6491934325031

c97

c97

cso30:c:InputInhibitor

--

true true true true

cso30:c:InputInhibitor

threshold

--

0

1,

--

Go back
539.0, 608.0

c98

c98

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back
830.416452246567, 673.0

c99

c99

cso30:c:InputProcess

--

true true true true

cso30:c:InputProcess

threshold

--

0

1,

--

Go back