Signal Transducer and Activator of Transcription (Stat)-Induced Stat Inhibitor 1 (Ssi-1)/Suppressor of Cytokine Signaling 1 (Socs1) Inhibits Insulin Signal Transduction Pathway through Modulating Insulin Receptor Substrate 1 (Irs-1) Phosphorylation

• Yoshinori Kawazoe

  aDepartment of Medicine III, Osaka 565-0871, Japan

• Tetsuji Naka

  aDepartment of Medicine III, Osaka 565-0871, Japan

• Minoru Fujimoto

  aDepartment of Medicine III, Osaka 565-0871, Japan

• Hidetsugu Kohzaki

  aDepartment of Medicine III, Osaka 565-0871, Japan

• Yoshiaki Morita

  aDepartment of Medicine III, Osaka 565-0871, Japan

• Masashi Narazaki

  aDepartment of Medicine III, Osaka 565-0871, Japan

• Kohichi Okumura

  eBiomolecular Engineering Research Institute, Osaka 565-0871, Japan

• Hiroshi Saitoh

  aDepartment of Medicine III, Osaka 565-0871, Japan

• Reiko Nakagawa

  aDepartment of Medicine III, Osaka 565-0871, Japan

• Yasuo Uchiyama

  bDepartment of Cell Biology and Anatomy I, Medical School, Osaka 565-0871, Japan

• Shizuo Akira

  cDepartment of Host Defense, Research Institute for Microbial Diseases, Osaka 565-0871, Japan

• Tadamitsu Kishimoto

  dOsaka University, Osaka 565-0871, Japan

抄録

Signal transducer and activator of transcription (STAT)-induced STAT inhibitor 1 (SSI-1) is known to function as a negative feedback regulator of cytokine signaling, but it is unclear whether it is involved in other biological events. Here, we show that SSI-1 participates and plays an important role in the insulin signal transduction pathway. SSI-1–deficient mice showed a significantly low level of blood sugar. While the forced expression of SSI-1 reduced the phosphorylation level of insulin receptor substrate 1 (IRS-1), SSI-1 deficiency resulted in sustained phosphorylation of IRS-1 in response to insulin. Furthermore, SSI-1 achieves this inhibition both by binding directly to IRS-1 and by suppressing Janus kinases. These findings suggest that SSI-1 acts as a negative feedback factor also in the insulin signal transduction pathway through the suppression of IRS-1 phosphorylation.

収録刊行物

• The Journal of Experimental Medicine

  The Journal of Experimental Medicine 193 (2), 263-270, 2001-01-15

  Rockefeller University Press

キーワード

• Immunology
• Immunology and Allergy

詳細情報

• CRID: 1363670320863488640
• NII論文ID: 30017415765
• DOI: 10.1084/jem.193.2.263
• ISSN: 15409538
• ISSN: 00221007
• ISSN: http://id.crossref.org/issn/00221007
• Web Site: https://rupress.org/jem/article-pdf/193/2/263/1700791/001372.pdf
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