Article

Molecular and Cellular Biochemistry

, Volume 182, Issue 1, pp 3-11

First online:

The IRS-signalling system: A network of docking proteins that mediate insulin action

  • Morris F. WhiteAffiliated withResearch Division, Joslin Diabetes Center and the Graduate Program in Biomedical and Biological Sciences, Harvard Medical School

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Abstract

New molecules discovered during the past ten years have created a rational framework to understand signalling transduction by a broad range of growth factors and cytokines, including insulin. Insulin action is initiated through the insulin receptor, a transmembrane glycoprotein with intrinsic protein tyrosine kinase activity. The tyrosine kinase mediates the insulin response through tyrosine phosphorylation of various cellular substrates, in particular the IRS-proteins. During insulin-stimulated tyrosine phosphorylation, the IRS-proteins mediate a broad biological response by binding and activating various enzymes or adapter molecules. Although we are far from a complete understanding of the insulin signalling system and its failure, enough pieces of the puzzle are falling into place that mechanism-based solutions to insulin resistance encountered with type II diabetes may soon be attainable.

IRS-1 proteins PI3-kinase Ras-MAP kinase SHP2 diabetes