Dataset Information

Yamada2003_JAK_STAT_SOCS1_knockout

ABSTRACT: 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 .

SUBMITTER: Sharat Vayttaden

PROVIDER: BIOMD0000000094 | BioModels | 2007-01-26

REPOSITORIES: BioModels

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Publications

Control mechanism of JAK/STAT signal transduction pathway.

Yamada Satoshi S Shiono Satoru S Joo Akiko A Yoshimura Akihiko A

FEBS letters 20030101 1-3

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-con ...[more]

PMID: 12527385

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Project description:Interferon-alpha (pegylated interferon and ribavirin) is used as standard-of-care therapeutic for chronic hepatitis C virus infection. Besides good cure in some patients other patients do not benefit from the treatment dependent on the virus type and host factors. One class of putative effector proteins is the family of Suppressors of cytokine signalling (SOCS). They act in a classical negative feedback-loop against the action of interferons and many other cytokines. It has been proven that some of them, in particular SOCS1 and SOCS3, inhibit the expression of interferon induced antiviral proteins. Their mode of action depends on the signal they are interfering with. In relation to the interferon-gamma pathway, they are thought to act on the interferon-alpha receptors by masking its recognition site for the Janus kinases (JAK), by blocking the kinase activity of the JAKs and coincidentally hindering STAT molecules from binding to the kinases. They are also thought to ubiquitinate the JAKs resulting in their proteosomal degradation. The function of SOCS proteins in suppressing the interferon-alpha pathway has not yet been characterized exhaustively. This study should unveil links to understand the resistance in interferon-alpha therapy. As results we got almost complete silencing of JAK-STAT signaling in SOCS1 over-expressing cells and tissue-dependent partially suppressed gene induction in SOCS3 over-expressing cell lines. Two human cancer cell lines (ME-15, HuH-7) were stably transfected with pcDNA3.1-SOCS plasmids in presence of geneticin and daughter cell lines were generated after singularization of cells. Next, original cell lines as well as SOCS1 and SOCS3 over-expressing cell lines were treated with 1000 U/ml interferon-alpha for 4 or 24 hours or in normal culture medium. Cells lines obtained from SOCS4 plasmid transfections were screened as additional control. Gene expression levels of cell cultured in control (0 for 4 hours, 2 for 24 hours) or interferon-alpha supplemented medium for 4 hours (1) or 24 hours (4) were analyzed. mRNA abundance was measured in triplicates using 12x8-sample commercial Illumina microarrays (HumanRef 8, version 3) and scanner system (iScan) as well as reagents recommend by Illumina (IlluminaM-BM-. TotalPrep Kit).

Dataset Information

Yamada2003_JAK_STAT_SOCS1_knockout

Publications

Control mechanism of JAK/STAT signal transduction pathway.

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