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.

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.
Mesh Terms:
Animals, Base Sequence, Carrier Proteins, DNA Primers, Feedback, Hypoglycemia, Insulin, Insulin Receptor Substrate Proteins, JNK Mitogen-Activated Protein Kinases, Mice, Mice, Knockout, Mitogen-Activated Protein Kinases, Phosphoproteins, Phosphorylation, RNA, Messenger, Repressor Proteins, Signal Transduction, Suppressor of Cytokine Signaling Proteins
J. Exp. Med.
Date: Jan. 15, 2001
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