Regulation of Protein Phosphorylation by Insulin and Insulin-Like Growth Factors in Cultured Fetal Neurons
Abundant evidence indicates that protein phosphorylation and dephosphorylation of tyrosine, serine, and threonine residues are key mechanisms by which insulin regulates cell function (for review see Ref. 1). The βsubunit of the insulin receptor is a tyrosine kinase activated by insulin binding that catalyzes autophosphorylation and phosphorylation of other proteins (2,3). The intrinsic tyrosine kinase activity of the insulin receptor appears to be critical for insulin action since cells transfected with kinase-deficient mutant insulin receptors (4) or cells injected with antibodies that inhibit the receptor kinase (5) become insensitive to insulin. A current working hypothesis is that activation of the insulin receptor kinase catalyzes the phosphorylation of tyrosine residues on several proteins. These proteins, in turn, regulate the more abundant serine kinases that phosphorylate proteins involved in the end-response.
KeywordsInsulin Receptor Neurite Outgrowth Serine Kinase Intrinsic Tyrosine Kinase Activity Insulin Receptor Kinase
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