The janus kinase inhibitor, JAB/SOCS-1, is an interferon-γ inducible gene and determines the sensitivity to interferons

Hiroshi Sakamoto, Ichiko Kinjyo, Akihiko Yoshimura

Research output: Contribution to journalReview article

24 Citations (Scopus)

Abstract

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-γ and forced expression of JAB/SOCS-1 conferred cells interferon resitance. This resistance was caused by inhibition of JAK1 and JAK2 activation in response to lFNγ. 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 IFNγ. Using in vitro mutagensis, we defined a functional structure of JAB/SOCS-1 and proposed a mechanism for how JAB inhibits JAK kinase activity.

Original languageEnglish
Pages (from-to)49-58
Number of pages10
JournalLeukemia and Lymphoma
Volume38
Issue number1-2
Publication statusPublished - 2000 May 9
Externally publishedYes

Keywords

  • CIS
  • Interferon γ
  • JAB
  • JAK
  • Negative regulation
  • SH2 domain
  • SOCS
  • SSI
  • STAT
  • Tyrosine kinase

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Fingerprint Dive into the research topics of 'The janus kinase inhibitor, JAB/SOCS-1, is an interferon-γ inducible gene and determines the sensitivity to interferons'. Together they form a unique fingerprint.

Cite this