BioModels Database logo

BioModels Database

spacer

BIOMD0000000094 - Yamada2003_JAK_STAT_SOCS1_knockout

 

 |   |   |  Send feedback
Reference Publication
Publication ID: 12527385
Yamada S, Shiono S, Joo A, Yoshimura A.
Control mechanism of JAK/STAT signal transduction pathway.
FEBS Lett. 2003 Jan; 534(1-3): 190-196
Advanced Technology R&D Center, Mitsubishi Electric Corporation, 8-1-1, Tsukaguchi-Honmachi, Amagasaki, Hyogo 661-8661, Japan. yamada.satoshi@wrc.melco.co.jp  [more]
Model
Original Model: DOQCS logo
Submitter: Sharat Vayttaden
Submission ID: MODEL4883413839
Submission Date: 13 Mar 2007 22:10:53 UTC
Last Modification Date: 27 Nov 2013 11:45:26 UTC
Creation Date: 26 Jan 2007 18:57:03 UTC
Encoders:  Harish Dharuri
set #1
bqbiol:occursIn Taxonomy Mus musculus
set #2
bqbiol:is KEGG Pathway mmu04630
Gene Ontology JAK-STAT cascade
set #3
bqmodel:isDerivedFrom BioModels Database Yamada2003_JAK_STAT_pathway
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

This model originates from BioModels Database: A Database of Annotated Published Models. It is copyright (c) 2005-2006 The BioModels Team.
For more information see the terms of use .

Model
Publication ID: 12527385 Submission Date: 13 Mar 2007 22:10:53 UTC Last Modification Date: 27 Nov 2013 11:45:26 UTC Creation Date: 26 Jan 2007 18:57:03 UTC
Mathematical expressions
Reactions
Receptor-JAK Binding Interferon-Receptor Binding IFN-Receptor complex dimerization INF-Receptor complex activation
Activated INFRJ2-STAT1c binding STAT1c activation Activated IFNRJ2-STAT1c binding Activated STAT1c dimerization
SHP2 binding IFNJR2 dephosphorylation Phosphorylated STAT1c-PPX binding STAT1c dephosphorylation
PPX binding STAT1c dimer dephosphorylation STAT1c-phosphorylated STAT1c binding STAT1c-nuclear transport
Phosphorylated STAT1n dimerization PPN binding STAT1n dephosphorylation PPN binding
STAT1n dephosphorylation STAT1n-phosphorylated STAT1n dimerization STAT1n transport to cytoplasm mRNA transport to cytoplasm
SOCS1 synthesis mRNAc degradation SOCS1 degradation phosphorylated IFNRJ2-SOCS1 binding
STAT1c binding SHP2 binding IFNRJ2 dephosphorylation SOCS1 unbinding
SHP2 binding STAT1c binding SHP2 binding v37
SOCS1 unbinding SOCS1 unbinding IFNRJ2 dephosphorylation SOCS1 unbinding
SOCS1 binding SOCS1 binding SOCS1 binding Interferon-receptor binding
IFNR-JAK binding      
Physical entities
Compartments Species
cytoplasm Receptor JAK Receptor JAK complex
Interferon-Receptor-JAK complex IFNRJ dimer Activated IFNRJ complex
STAT1c IFNRJ2_star_STAT1c STAT1c_star
IFNRJ2_star_STAT1c_star STAT1c_star_STAT1c_star SHP2
IFNRJ2_star_SHP2 PPX STAT1c_star_PPX
STAT1c_STAT1c_star mRNAc SOCS1
IFNRJ2_star_SOCS1 IFNRJ2_star_SHP2_SOCS1_STAT1c STAT1c_star_STAT1c_star_PPX
IFNRJ2_star_SOCS1_STAT1c IFN IFNRJ2_star_SHP2_STAT1c
IFNRJ2_star_SHP2_SOCS1 IFNR  
nucleus STAT1n_star_STAT1n_star STAT1n_star PPN
STAT1n_star_PPN STAT1n STAT1n_STAT1n_star
mRNAn STAT1n_star_STAT1n_star_PPN  
Reactions (45)
 
 Receptor-JAK Binding [JAK] + [Receptor] → [Receptor JAK complex];  
 
 Interferon-Receptor Binding [Receptor JAK complex] + [IFN] → [Interferon-Receptor-JAK complex];  
 
 IFN-Receptor complex dimerization 2.0 × [Interferon-Receptor-JAK complex] → [IFNRJ dimer];  
 
 INF-Receptor complex activation [IFNRJ dimer] → [Activated IFNRJ complex];  
 
 Activated INFRJ2-STAT1c binding [Activated IFNRJ complex] + [STAT1c] → [IFNRJ2_star_STAT1c];  
 
 STAT1c activation [IFNRJ2_star_STAT1c] → [STAT1c_star] + [Activated IFNRJ complex];  
 
 Activated IFNRJ2-STAT1c binding [STAT1c_star] + [Activated IFNRJ complex] → [IFNRJ2_star_STAT1c_star];  
 
 Activated STAT1c dimerization 2.0 × [STAT1c_star] → [STAT1c_star_STAT1c_star];  
 
 SHP2 binding [SHP2] + [Activated IFNRJ complex] → [IFNRJ2_star_SHP2];  
 
 IFNJR2 dephosphorylation [IFNRJ2_star_SHP2] → [SHP2] + [IFNRJ dimer];  
 
 Phosphorylated STAT1c-PPX binding [STAT1c_star] + [PPX] → [STAT1c_star_PPX];  
 
 STAT1c dephosphorylation [STAT1c_star_PPX] → [STAT1c] + [PPX];  
 
 PPX binding [STAT1c_star_STAT1c_star] + [PPX] → [STAT1c_star_STAT1c_star_PPX];  
 
 STAT1c dimer dephosphorylation [STAT1c_star_STAT1c_star_PPX] → [STAT1c_STAT1c_star] + [PPX];  
 
 STAT1c-phosphorylated STAT1c binding [STAT1c_star] + [STAT1c] → [STAT1c_STAT1c_star];  
 
 STAT1c-nuclear transport [STAT1c_star_STAT1c_star] → [STAT1n_star_STAT1n_star];  
 
 Phosphorylated STAT1n dimerization 2.0 × [STAT1n_star] → [STAT1n_star_STAT1n_star];  
 
 PPN binding [STAT1n_star] + [PPN] → [STAT1n_star_PPN];  
 
 STAT1n dephosphorylation [STAT1n_star_PPN] → [STAT1n] + [PPN];  
 
 PPN binding [STAT1n_star_STAT1n_star] + [PPN] → [STAT1n_star_STAT1n_star_PPN];  
 
 STAT1n dephosphorylation [STAT1n_star_STAT1n_star_PPN] → [STAT1n_STAT1n_star] + [PPN];  
 
 STAT1n-phosphorylated STAT1n dimerization [STAT1n_star] + [STAT1n] → [STAT1n_STAT1n_star];  
 
 STAT1n transport to cytoplasm [STAT1n] → [STAT1c];  
 
 mRNA transport to cytoplasm [mRNAn] → [mRNAc];  
 
 SOCS1 synthesis  → [SOCS1];   {mRNAc}
 
 mRNAc degradation [mRNAc] → ;  
 
 SOCS1 degradation [SOCS1] → ;  
 
 phosphorylated IFNRJ2-SOCS1 binding [Activated IFNRJ complex] + [SOCS1] → [IFNRJ2_star_SOCS1];  
 
 STAT1c binding [IFNRJ2_star_SOCS1] + [STAT1c] → [IFNRJ2_star_SOCS1_STAT1c];  
 
 SHP2 binding [IFNRJ2_star_SOCS1_STAT1c] + [SHP2] → [IFNRJ2_star_SHP2_SOCS1_STAT1c];  
 
 IFNRJ2 dephosphorylation [IFNRJ2_star_SHP2_SOCS1_STAT1c] → [IFNRJ dimer] + [SOCS1] + [STAT1c] + [SHP2];  
 
 SOCS1 unbinding [IFNRJ2_star_SHP2_SOCS1_STAT1c] → [IFNRJ2_star_SHP2_STAT1c];  
 
 SHP2 binding [IFNRJ2_star_SOCS1] + [SHP2] → [IFNRJ2_star_SHP2_SOCS1];  
 
 STAT1c binding [IFNRJ2_star_SHP2_SOCS1] + [STAT1c] → [IFNRJ2_star_SHP2_SOCS1_STAT1c];  
 
 SHP2 binding [IFNRJ2_star_STAT1c] + [SHP2] → [IFNRJ2_star_SHP2_STAT1c];  
 
 v37 [IFNRJ2_star_SHP2_STAT1c] → [STAT1c] + [SHP2] + [IFNRJ dimer];  
 
 SOCS1 unbinding [IFNRJ2_star_SOCS1_STAT1c] → [IFNRJ2_star_STAT1c];  
 
 SOCS1 unbinding [IFNRJ2_star_SHP2_SOCS1] → [IFNRJ2_star_SHP2];  
 
 IFNRJ2 dephosphorylation [IFNRJ2_star_SHP2_SOCS1] → [SHP2] + [IFNRJ dimer] + [SOCS1];  
 
 SOCS1 unbinding [IFNRJ2_star_SOCS1] → [Activated IFNRJ complex];  
 
 SOCS1 binding [IFNRJ2_star_STAT1c] + [SOCS1] → [IFNRJ2_star_SOCS1_STAT1c];  
 
 SOCS1 binding [IFNRJ2_star_SHP2] + [SOCS1] → [IFNRJ2_star_SHP2_SOCS1];  
 
 SOCS1 binding [IFNRJ2_star_SHP2_STAT1c] + [SOCS1] → [IFNRJ2_star_SHP2_SOCS1_STAT1c];  
 
 Interferon-receptor binding [Receptor] + [IFN] → [IFNR];  
 
 IFNR-JAK binding [JAK] + [IFNR] → [Interferon-Receptor-JAK complex];  
 
 cytoplasm Spatial dimensions: 3.0  Compartment size: 1.0
 
 Receptor
Compartment: cytoplasm
Initial concentration: 10.0
 
 JAK
Compartment: cytoplasm
Initial concentration: 10.0
 
 Receptor JAK complex
Compartment: cytoplasm
Initial concentration: 0.0
 
 Interferon-Receptor-JAK complex
Compartment: cytoplasm
Initial concentration: 0.0
 
 IFNRJ dimer
Compartment: cytoplasm
Initial concentration: 0.0
 
 Activated IFNRJ complex
Compartment: cytoplasm
Initial concentration: 0.0
 
 STAT1c
Compartment: cytoplasm
Initial concentration: 1000.0
 
 IFNRJ2_star_STAT1c
Compartment: cytoplasm
Initial concentration: 0.0
 
 STAT1c_star
Compartment: cytoplasm
Initial concentration: 0.0
 
 IFNRJ2_star_STAT1c_star
Compartment: cytoplasm
Initial concentration: 0.0
 
 STAT1c_star_STAT1c_star
Compartment: cytoplasm
Initial concentration: 0.0
 
 SHP2
Compartment: cytoplasm
Initial concentration: 100.0
 
 IFNRJ2_star_SHP2
Compartment: cytoplasm
Initial concentration: 0.0
 
   PPX
Compartment: cytoplasm
Initial concentration: 50.0
 
 STAT1c_star_PPX
Compartment: cytoplasm
Initial concentration: 0.0
 
 STAT1c_STAT1c_star
Compartment: cytoplasm
Initial concentration: 0.0
 
 mRNAc
Compartment: cytoplasm
Initial concentration: 0.0
 
 SOCS1
Compartment: cytoplasm
Initial concentration: 0.0
 
 IFNRJ2_star_SOCS1
Compartment: cytoplasm
Initial concentration: 0.0
 
 IFNRJ2_star_SHP2_SOCS1_STAT1c
Compartment: cytoplasm
Initial concentration: 0.0
 
 STAT1c_star_STAT1c_star_PPX
Compartment: cytoplasm
Initial concentration: 0.0
 
 IFNRJ2_star_SOCS1_STAT1c
Compartment: cytoplasm
Initial concentration: 0.0
 
 IFN
Compartment: cytoplasm
Initial concentration: 10.0
Constant
 
 IFNRJ2_star_SHP2_STAT1c
Compartment: cytoplasm
Initial concentration: 0.0
 
 IFNRJ2_star_SHP2_SOCS1
Compartment: cytoplasm
Initial concentration: 0.0
 
 IFNR
Compartment: cytoplasm
Initial concentration: 0.0
 
 nucleus Spatial dimensions: 3.0  Compartment size: 1.0
 
 STAT1n_star_STAT1n_star
Compartment: nucleus
Initial concentration: 0.0
 
 STAT1n_star
Compartment: nucleus
Initial concentration: 0.0
 
   PPN
Compartment: nucleus
Initial concentration: 60.0
 
 STAT1n_star_PPN
Compartment: nucleus
Initial concentration: 0.0
 
 STAT1n
Compartment: nucleus
Initial concentration: 0.0
 
 STAT1n_STAT1n_star
Compartment: nucleus
Initial concentration: 0.0
 
 mRNAn
Compartment: nucleus
Initial concentration: 0.0
 
 STAT1n_star_STAT1n_star_PPN
Compartment: nucleus
Initial concentration: 0.0
 
Receptor-JAK Binding (2)
 
   kf
Value: 0.1   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.05   (Units: sec_inv)
Constant
 
Interferon-Receptor Binding (2)
 
   kf
Value: 0.02   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.02   (Units: sec_inv)
Constant
 
IFN-Receptor complex dimerization (2)
 
   kf
Value: 0.04   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.2   (Units: sec_inv)
Constant
 
INF-Receptor complex activation (1)
 
   kf
Value: 0.0050   (Units: sec_inv)
Constant
 
Activated INFRJ2-STAT1c binding (2)
 
   kf
Value: 0.0080   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.8   (Units: sec_inv)
Constant
 
STAT1c activation (1)
 
   kf
Value: 0.4   (Units: sec_inv)
Constant
 
Activated IFNRJ2-STAT1c binding (2)
 
   kf
Value: 0.0050   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.5   (Units: sec_inv)
Constant
 
Activated STAT1c dimerization (2)
 
   kf
Value: 0.02   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.1   (Units: sec_inv)
Constant
 
SHP2 binding (2)
 
   kf
Value: 0.0010   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.2   (Units: sec_inv)
Constant
 
IFNJR2 dephosphorylation (1)
 
   kf
Value: 0.0030   (Units: sec_inv)
Constant
 
Phosphorylated STAT1c-PPX binding (2)
 
   kf
Value: 0.0010   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.2   (Units: sec_inv)
Constant
 
STAT1c dephosphorylation (1)
 
   kf
Value: 0.0030   (Units: sec_inv)
Constant
 
PPX binding (2)
 
   kf
Value: 0.0010   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.2   (Units: sec_inv)
Constant
 
STAT1c dimer dephosphorylation (1)
 
   kf
Value: 0.0030   (Units: sec_inv)
Constant
 
STAT1c-phosphorylated STAT1c binding (2)
 
   kf
Value: 2.0E-7   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.2   (Units: sec_inv)
Constant
 
STAT1c-nuclear transport (1)
 
   kf
Value: 0.0050   (Units: sec_inv)
Constant
 
Phosphorylated STAT1n dimerization (2)
 
   kf
Value: 0.02   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.1   (Units: sec_inv)
Constant
 
PPN binding (2)
 
   kf
Value: 0.0010   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.2   (Units: sec_inv)
Constant
 
STAT1n dephosphorylation (1)
 
   kf
Value: 0.0050   (Units: sec_inv)
Constant
 
PPN binding (2)
 
   kf
Value: 0.0010   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.2   (Units: sec_inv)
Constant
 
STAT1n dephosphorylation (1)
 
   kf
Value: 0.0050   (Units: sec_inv)
Constant
 
STAT1n-phosphorylated STAT1n dimerization (2)
 
   kf
Value: 2.0E-7   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.2   (Units: sec_inv)
Constant
 
STAT1n transport to cytoplasm (1)
 
   kf
Value: 0.05   (Units: sec_inv)
Constant
 
mRNA transport to cytoplasm (1)
 
   kf
Value: 0.0010   (Units: sec_inv)
Constant
 
SOCS1 synthesis (1)
 
   kf
Value: 0.01   (Units: sec_inv)
Constant
 
mRNAc degradation (1)
 
   kf
Value: 5.0E-4   (Units: sec_inv)
Constant
 
SOCS1 degradation (1)
 
   kf
Value: 5.0E-4   (Units: sec_inv)
Constant
 
phosphorylated IFNRJ2-SOCS1 binding (2)
 
   kf
Value: 0.02   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.1   (Units: sec_inv)
Constant
 
STAT1c binding (2)
 
   kf
Value: 0.0080   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.8   (Units: sec_inv)
Constant
 
SHP2 binding (2)
 
   kf
Value: 0.0010   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.2   (Units: sec_inv)
Constant
 
IFNRJ2 dephosphorylation (1)
 
   kf
Value: 0.0030   (Units: sec_inv)
Constant
 
SOCS1 unbinding (1)
 
   kf
Value: 5.0E-4   (Units: sec_inv)
Constant
 
SHP2 binding (2)
 
   kf
Value: 0.0010   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.2   (Units: sec_inv)
Constant
 
STAT1c binding (2)
 
   kf
Value: 0.0080   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.8   (Units: sec_inv)
Constant
 
SHP2 binding (2)
 
   kf
Value: 0.0010   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.2   (Units: sec_inv)
Constant
 
v37 (1)
 
   kf
Value: 0.0030   (Units: sec_inv)
Constant
 
SOCS1 unbinding (1)
 
   kf
Value: 5.0E-4   (Units: sec_inv)
Constant
 
SOCS1 unbinding (1)
 
   kf
Value: 5.0E-4   (Units: sec_inv)
Constant
 
IFNRJ2 dephosphorylation (1)
 
   kf
Value: 0.0030   (Units: sec_inv)
Constant
 
SOCS1 unbinding (1)
 
   kf
Value: 5.0E-4   (Units: sec_inv)
Constant
 
SOCS1 binding (2)
 
   kf
Value: 0.02   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.1   (Units: sec_inv)
Constant
 
SOCS1 binding (2)
 
   kf
Value: 0.02   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.1   (Units: sec_inv)
Constant
 
SOCS1 binding (2)
 
   kf
Value: 0.02   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.1   (Units: sec_inv)
Constant
 
Interferon-receptor binding (2)
 
   kf
Value: 0.02   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.02   (Units: sec_inv)
Constant
 
IFNR-JAK binding (2)
 
   kf
Value: 0.1   (Units: nM_inv_sec_inv)
Constant
 
   kb
Value: 0.05   (Units: sec_inv)
Constant
 
Representative curation result(s)
Representative curation result(s) of BIOMD0000000094

Curator's comment: (updated: 13 Mar 2007 00:12:03 GMT)

The plots correspond to SOCS1 knockout time profiles in Fig 2 of the paper. Simulation results obtained from MathSBML.

spacer
spacer