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 journalArticle

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
Externally publishedYes

Fingerprint

Janus Kinases
Interferons
STAT Transcription Factors
Cytokine Receptors
Knockout Mice
Protein-Tyrosine Kinases
Genes
Cell Differentiation
Signal Transduction
Cytokines
Growth
Proteins
In Vitro Techniques

Keywords

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

ASJC Scopus subject areas

  • Hematology
  • Oncology
  • Cancer Research

Cite this

The janus kinase inhibitor, JAB/SOCS-1, is an interferon-γ inducible gene and determines the sensitivity to interferons. / Sakamoto, Hiroshi; Kinjyo, Ichiko; Yoshimura, Akihiko.

In: Leukemia and Lymphoma, Vol. 38, No. 1-2, 2000, p. 49-58.

Research output: Contribution to journalArticle

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