Ser/Thr Phosphorylation of IRS Proteins: A Molecular Basis for Insulin Resistance

Sci. STKE, 25 January 2005
Vol. 2005, Issue 268, p. pe4
DOI: 10.1126/stke.2682005pe4

Ser/Thr Phosphorylation of IRS Proteins: A Molecular Basis for Insulin Resistance

  1. Yehiel Zick*
  1. Department of Molecular Cell Biology, Weizmann Institute of Science, Rehovot 76100, Israel.
  1. *Corresponding author. E-mail: yehiel.zick{at}


S6K1, like other serine and threonine kinases activated by insulin (such as mTOR and PKCζ), has recently been shown to participate in negative feedback mechanisms aimed at terminating insulin signaling through IRS (insulin receptor substrate) phosphorylation. Such homeostatic mechanisms can also be activated by excess nutrients or inducers of insulin resistance (such as fatty acids and proinflammatory cytokines) to produce an insulin-resistant state that often leads to the development of diabetes. Identification of the specific kinases involved in such insulin resistance pathways can help lead to the rational design of novel therapeutic agents for treating insulin resistance and type 2 diabetes.


Y. Zick, Ser/Thr Phosphorylation of IRS Proteins: A Molecular Basis for Insulin Resistance. Sci. STKE 2005, pe4 (2005).

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