JAB/SOCS1/SSI-1 is an interleukin-2-induced inhibitor of IL-2 signaling

Bernhard Sporri, Panu E. Kovanen, Atsuo Sasaki, Akihiko Yoshimura, Warren J. Leonard

Research output: Contribution to journalArticle

93 Citations (Scopus)

Abstract

JAB/suppressor of cytokine signaling 1 (SOCS1) STAT-induced STAT inhibitor-1 (SSI-1) (JAB/SOCS1/SSI-1) is an SH2-domain-containing protein that is induced by and negatively regulates signaling by a number of cytokines including interleukin-4 (IL-4), IL-6, interferon (IFN)-γ, prolactin, growth hormone, and erythropoietin. The role of JAB/SOCS1/SSI-1 in IL-2 signaling has been analyzed. JAB/SOCS1/SSI-1 is strongly induced by IL-2 in peripheral blood T cells, and JAB/SOCS1/SSI-1 overexpression strongly inhibits IL-2-induced signal transducer and activator of transcription-5 (Stat5) phosphorylation and transcriptional activity. In cotransfection experiments, JAB/SOCS1/SSI-1 associates with both Jak1 and Jak3; however, JAB/SOCS1/SSI-1 had a greater effect on Jak1 tyrosine phosphorylation and kinase activity. JAB/SOCS1/SSI-1 also interacts with IL-2Rβ, and this interaction requires the A region (residues 313-382) of IL-2Rβ. However, this interaction was not essential for the inhibitory action of JAB. Thus, JAB/SOCS1/SSI-1 is an IL-2-induced inhibitor of IL-2 signaling that functions by inhibiting Jak kinase activity. This suggests an important role for JAB/SOCS1/SSI-1 in regulating T-cell responses.

Original languageEnglish
Pages (from-to)221-226
Number of pages6
JournalBlood
Volume97
Issue number1
DOIs
Publication statusPublished - 2001 Jan 1
Externally publishedYes

ASJC Scopus subject areas

  • Biochemistry
  • Immunology
  • Hematology
  • Cell Biology

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