Dynamin associates with Src-Homology Collagen (Shc) and becomes tyrosine phosphorylated in response to insulin.
The activated insulin receptor phosphorylates docking proteins such as Src-Homology Collagen (Shc) and Insulin Receptor Substrate-1 (IRS-1), which then bind several proteins that contain a Src-Homology 2 (SH2) domain. Both Shc and IRS-1 associate with Growth Factor Receptor-Bound protein 2 (Grb2), an adaptor molecule. The hormone-receptor complex is then rapidly internalized through coated-pits. Dynamin, a 100 kDa protein with GTPase activity, is thought to play a crucial role in receptor-mediated endocytosis. In this study, we show that insulin induces tyrosine phosphorylation of dynamin in cells overexpressing human insulin receptors. Phosphorylation is observed rapidly, i.e. within 1 minute of insulin treatment. Moreover, exposure of cells to the hormone leads to co-immunoprecipitation of dynamin with Shc and with insulin receptor. Since dynamin constitutively associates with Grb2, it could be recruited to the insulin signaling complex through binding of Grb2 to tyrosine-phosphorylated Shc.
Baron
V
V
Institut National de la Santé et de la Recherche Médicale U145, Faculté de Médecine, Nice, France.
Alengrin
F
F
Van Obberghen
E
E
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D000818:Animals; D002460:Cell Line; D034281:Dynamins; D005347:Fibroblasts / Q000187:drug effects / Q000378:metabolism; D020558:GTP Phosphohydrolases / Q000378:metabolism*; D006801:Humans; D007328:Insulin / Q000494:pharmacology*; D010766:Phosphorylation; D011233:Precipitin Tests; D011506:Proteins / Q000378:metabolism*; D051381:Rats / Q000196:embryology; D011972:Receptor, Insulin / Q000378:metabolism; D055765:Shc Signaling Adaptor Proteins; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014443:Tyrosine / Q000378:metabolism*
D048868:Adaptor Proteins, Signal Transducing; D033942:Adaptor Proteins, Vesicular Transport; D007328:Insulin; D011506:Proteins; C528024:SHC1 protein, human; D055765:Shc Signaling Adaptor Proteins; C528035:Shc1 protein, rat; D000071425:Src Homology 2 Domain-Containing, Transforming Protein 1; D014443:Tyrosine; D011972:Receptor, Insulin; D020558:GTP Phosphohydrolases; D034281:Dynamins