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yamada2

yamada2

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v1

Receptor-JAK Binding

JAK + R > RJ

v10

IFNJR2 dephosphorylation

IFNRJ2_star_SHP2 > SHP2 + IFNRJ2

v11

Phosphorylated STAT1c-PPX binding

STAT1c_star + PPX > STAT1c_star_PPX

v12

STAT1c dephosphorylation

STAT1c_star_PPX > STAT1c + PPX

v13

PPX binding

STAT1c_star_STAT1c_star + PPX > STAT1c_star_STAT1c_star_PPX

v14

STAT1c dimer dephosphorylation

STAT1c_star_STAT1c_star_PPX > STAT1c_STAT1c_star + PPX

v15

STAT1c-phosphorylated STAT1c binding

STAT1c_star + STAT1c > STAT1c_STAT1c_star

v16

STAT1c-nuclear transport

STAT1c_star_STAT1c_star > STAT1n_star_STAT1n_star

v17

Phosphorylated STAT1n dimerization

{2.0}STAT1n_star > STAT1n_star_STAT1n_star

v18

PPN binding

STAT1n_star + PPN > STAT1n_star_PPN

v19

STAT1n dephosphorylation

STAT1n_star_PPN > STAT1n + PPN

v2

Interferon-Receptor Binding

RJ + IFN > IFNRJ

v20

PPN binding

STAT1n_star_STAT1n_star + PPN > STAT1n_star_STAT1n_star_PPN

v21

STAT1n dephosphorylation

STAT1n_star_STAT1n_star_PPN > STAT1n_STAT1n_star + PPN

v22

STAT1n-phosphorylated STAT1n dimerization

STAT1n_star + STAT1n > STAT1n_STAT1n_star

v23

STAT1n transport to cytoplasm

STAT1n > STAT1c

v25

mRNA transport to cytoplasm

mRNAn > mRNAc

v26

SOCS1 synthesis

∅ > SOCS1

v27

mRNAc degradation

mRNAc > ∅

v28

SOCS1 degradation

SOCS1 > ∅

v29

phosphorylated IFNRJ2-SOCS1 binding

IFNRJ2_star + SOCS1 > IFNRJ2_star_SOCS1

v3

IFN-Receptor complex dimerization

{2.0}IFNRJ > IFNRJ2

v30

STAT1c binding

IFNRJ2_star_SOCS1 + STAT1c > IFNRJ2_star_SOCS1_STAT1c

v31

SHP2 binding

IFNRJ2_star_SOCS1_STAT1c + SHP2 > IFNRJ2_star_SHP2_SOCS1_STAT1c

v32

IFNRJ2 dephosphorylation

IFNRJ2_star_SHP2_SOCS1_STAT1c > IFNRJ2 + SOCS1 + STAT1c + SHP2

v33

SOCS1 unbinding

IFNRJ2_star_SHP2_SOCS1_STAT1c > IFNRJ2_star_SHP2_STAT1c

v34

SHP2 binding

IFNRJ2_star_SOCS1 + SHP2 > IFNRJ2_star_SHP2_SOCS1

v35

STAT1c binding

IFNRJ2_star_SHP2_SOCS1 + STAT1c > IFNRJ2_star_SHP2_SOCS1_STAT1c

v36

SHP2 binding

IFNRJ2_star_STAT1c + SHP2 > IFNRJ2_star_SHP2_STAT1c

v37

IFNRJ2_star_SHP2_STAT1c > STAT1c + SHP2 + IFNRJ2

v38

SOCS1 unbinding

IFNRJ2_star_SOCS1_STAT1c > IFNRJ2_star_STAT1c

v39

SOCS1 unbinding

IFNRJ2_star_SHP2_SOCS1 > IFNRJ2_star_SHP2

v4

INF-Receptor complex activation

IFNRJ2 > IFNRJ2_star

v40

IFNRJ2 dephosphorylation

IFNRJ2_star_SHP2_SOCS1 > SHP2 + IFNRJ2 + SOCS1

v41

SOCS1 unbinding

IFNRJ2_star_SOCS1 > IFNRJ2_star

v42

SOCS1 binding

IFNRJ2_star_STAT1c + SOCS1 > IFNRJ2_star_SOCS1_STAT1c

v43

SOCS1 binding

IFNRJ2_star_SHP2 + SOCS1 > IFNRJ2_star_SHP2_SOCS1

v44

SOCS1 binding

IFNRJ2_star_SHP2_STAT1c + SOCS1 > IFNRJ2_star_SHP2_SOCS1_STAT1c

v45

Interferon-receptor binding

R + IFN > IFNR

v46

IFNR-JAK binding

JAK + IFNR > IFNRJ

v5

Activated INFRJ2-STAT1c binding

IFNRJ2_star + STAT1c > IFNRJ2_star_STAT1c

v6

STAT1c activation

IFNRJ2_star_STAT1c > STAT1c_star + IFNRJ2_star

v7

Activated IFNRJ2-STAT1c binding

STAT1c_star + IFNRJ2_star > IFNRJ2_star_STAT1c_star

v8

Activated STAT1c dimerization

{2.0}STAT1c_star > STAT1c_star_STAT1c_star

v9

SHP2 binding

SHP2 + IFNRJ2_star > IFNRJ2_star_SHP2

Parameters

Global parameters
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v3
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v4
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Fixed species

Initial values

Functions and Rules

Events

Constraints

Note that constraints are not enforced in simulations. It remains the responsibility of the user to verify that simulation results satisfy these constraints.


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Control mechanism of JAK/STAT signal transduction pathway.

  • Satoshi Yamada
  • Satoru Shiono
  • Akiko Joo
  • Akihiko Yoshimura
FEBS Lett. 2003; 534 : 190-196
Abstract
Suppressor of cytokine signaling-1 (SOCS1) was identified as the negative regulator of Janus kinase (JAK) and signal transducer and activator of transcription (STAT) signal transduction pathway. However, the kinetics and control mechanism of the pathway have not yet been fully understood. We have developed the computer simulation of the JAK/STAT pathway. Without nuclear phosphatase, SOCS1's binding to JAK did not cause the decrease in nuclear phosphorylated STAT1. However, without SH2 domain-containing tyrosine phosphatase 2 (SHP-2) or cytoplasmic phosphatase, it did. So nuclear phosphatase is considered to be the most important in this system. By changing parameters of the model, dynamical characteristics and control mechanism were investigated.
The SBML for this model was obtained from the BioModels database (BioModels ID: BIOMD0000000094). Biomodels notes: "NCBS Curation Comments: This model shows the control mechanism of Jak-Stat pathway, here SOCS1 (Suppressor of cytokine signaling-I) was identified as the negative regulator of Jak and STAT signal transduction pathway. This is the knockout version of Jak-Stat pathway in this model the SOCS1 has been knocked out i.e it formation is not shown. The graphs are almost similar to the graphs as shown in the paper but STAT1n graph has some ambiguities. Thanks to Dr Satoshi Yamada for clarifying some of those ambiguities and providing the values used in simulations. Biomodels Curation Comments: The model reproduces the figures 2 (B,D,F,H,J,L,N) corresponding to JAK/STAT activation in SOCS1 knock out cells. The model was successfully tested on MathSBML" JWS Online curation: This model was curated by reproducing the figures 2 (B,D,F) as described in the BioModels Notes. No additional changes were made.