Focal adhesion kinase and Src mediate integrin regulation of insulin receptor phosphorylation.
We show here that phosphorylation of the insulin receptor and insulin receptor substrate-1 is increased when suspended cells are replated on fibronectin. This is not due to decreased numbers of cell surface receptors, alteration of insulin binding, or stimulation of a phosphatase activity in non-adherent cells. Expression of Src together with focal adhesion kinase (FAK) in suspended cells restores insulin-induced receptor autophosphorylation to levels observed in fibronectin-attached cells. Conversely, expression of dominant-negative mutants of either Src or FAK abolishes potentiation of insulin receptor phosphorylation by cell adhesion. The results suggest that both Src and FAK participate in integrin-mediated regulation of insulin receptor signal.
El Annabi
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S
Institut National de la Santé et de la Recherche Médicale, U145/IFR 50, Faculté de Médecine, Avenue de Valombrose, 06107 Cedex 02, Nice, France.
Gautier
N
N
Baron
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V
D000818:Animals; D000911:Antibodies, Monoclonal / Q000494:pharmacology; D016466:CHO Cells; D002448:Cell Adhesion / Q000187:drug effects / Q000502:physiology; D002478:Cells, Cultured; D006224:Cricetinae; D005353:Fibronectins / Q000378:metabolism; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; D006801:Humans; D007328:Insulin / Q000494:pharmacology; D055504:Insulin Receptor Substrate Proteins; D051379:Mice; D009154:Mutation; D010750:Phosphoproteins / Q000378:metabolism; D010766:Phosphorylation / Q000187:drug effects; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011972:Receptor, Insulin / Q000235:genetics / Q000276:immunology / Q000378:metabolism*; D019061:src-Family Kinases / Q000235:genetics / Q000378:metabolism*
D000911:Antibodies, Monoclonal; D005353:Fibronectins; C526292:IRS1 protein, human; D007328:Insulin; D055504:Insulin Receptor Substrate Proteins; C526295:Irs1 protein, mouse; D010750:Phosphoproteins; D011505:Protein-Tyrosine Kinases; D011972:Receptor, Insulin; D051417:Focal Adhesion Kinase 1; D051416:Focal Adhesion Protein-Tyrosine Kinases; C496050:PTK2 protein, human; C496051:Ptk2 protein, mouse; D019061:src-Family Kinases