The IRS-signalling system: a network of docking proteins that mediate insulin action.
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.
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MF
Research Division, Joslin Diabetes Center, Harvard Medical School, Boston, MA 02215, USA.
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D004268:DNA-Binding Proteins; D006801:Humans; D007328:Insulin / Q000502:physiology*; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; D010750:Phosphoproteins / Q000502:physiology*; D016601:RNA-Binding Proteins; D011972:Receptor, Insulin / Q000502:physiology*; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D004268:DNA-Binding Proteins; C489560:DOK1 protein, human; C489561:Dok1 protein, mouse; C098587:GAB1 protein, human; C074561:GAP-associated protein p62; C490897:Gab1 protein, mouse; C526292:IRS1 protein, human; C526297:IRS2 protein, human; C491585:IRS3P protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; D047908:Intracellular Signaling Peptides and Proteins; C526295:Irs1 protein, mouse; C526298:Irs2 protein, mouse; D010750:Phosphoproteins; D016601:RNA-Binding Proteins; D011972:Receptor, Insulin