The janus kinase inhibitor, Jab/SOCS-1, is an interferon-gamma inducible gene and determines the sensitivity to interferons.
The Janus family of protein tyrosine kinases (JAKs) and STAT transcription factors regulate cellular processes involved in cell growth, differentiation, and transformation through their association with cytokine receptors. The CIS family of proteins (also referred as the SOCS or SSI family) has been implicated in the regulation of signal transduction by a variety of cytokines. Among them, we have shown that JAB/SOCS-1 is strongly induced by interferon-gamma and forced expression of JAB/SOCS-1I conferred cells interferon resistance. This resistance was caused by inhibition of JAK1 and JAK2 activation in response to IFNgamma. Moreover, recent detailed analysis of JAB/SOCS-1 knockout mice revealed that JAB/SOCS-1 is indeed a "negative feedback regulator" that determine the sensitivity of cells to IFNgamma. Using in vitro mutagensis, we defined a functional structure of JAB/SOCS-1 and proposed a mechanism for how JAB inhibits JAK kinase activity.
Sakamoto
H
H
Institute of Life Science, Kurume University, Japan.
Kinjyo
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I
Yoshimura
A
A
D016475:3T3 Cells; D000818:Animals; D002352:Carrier Proteins / Q000235:genetics*; D004361:Drug Tolerance / Q000235:genetics; D005786:Gene Expression Regulation; D006801:Humans; D007371:Interferon-gamma / Q000235:genetics*; D007372:Interferons / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D011505:Protein-Tyrosine Kinases / Q000037:antagonists & inhibitors / Q000235:genetics; D012097:Repressor Proteins; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins
D002352:Carrier Proteins; D047908:Intracellular Signaling Peptides and Proteins; D012097:Repressor Proteins; C108944:SOCS1 protein, human; C491590:Socs1 protein, mouse; D000071222:Suppressor of Cytokine Signaling 1 Protein; D050826:Suppressor of Cytokine Signaling Proteins; D007371:Interferon-gamma; D007372:Interferons; D011505:Protein-Tyrosine Kinases