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

Overview

Journal J Exp Med

Specialties Allergy & Immunology
General Medicine

Date 2001 Feb 24

PMID 11208867

Citations 44

Authors

Y Kawazoe

T Naka

M Fujimoto

H Kohzaki

Y Morita

M Narazaki

K Okumura

H Saitoh

R Nakagawa

Y Uchiyama

S Akira

T Kishimoto

Affiliations

Soon will be listed here.

Abstract

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.

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