Insulin-like growth factor-1 stimulation of cells induces formation of complexes containing phosphatidylinositol-3-kinase, guanosine triphosphatase-activating protein (GAP), and p62 GAP-associated protein.
The insulin-like growth factor-1 (IGF-1) receptor is structurally related to the insulin receptor and shares common features in receptor signaling. These features include receptor autophosphorylation, phosphorylation of insulin receptor substrate-1, and activation of Ras and phosphatidylinositol-3-kinase (PI3K). Previously, we reported that after insulin treatment of rat HTC cells expressing human insulin receptors, a unique insulin receptor signaling complex was formed that contained the insulin receptor, the p85 subunit of PI3K, GTPase-activating protein (GAP), and p62 GAP-associated protein. In the present study, using wild type HTC cells, we investigated whether the activated IGF-1 receptor also forms a similar signaling complex. To study the proteins present in IGF-1 receptor signaling complexes, we used immunoprecipitation and Western blotting analysis with appropriate antibodies. In response to IGF-1, insulin receptor substrate-1 was tyrosine phosphorylated and formed a complex with the PI3K heterodimer that consists of a p85 regulatory subunit and a p110 catalytic subunit. In addition, a separate complex was formed, consisting of p85, p62 GAP-associated protein and GAP. The p62 in this complex was tyrosine phosphorylated. These studies suggest, therefore, that the IGF-1 receptor, like the insulin receptor, induces the formation of multiple signaling complexes that most likely mediate the proliferative effects of these receptors.
Sánchez-Margalet
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V
Department of Medicine, Mount Zion Medical Center of the University of California, San Francisco 94115.
Zoratti
R
R
Sung
C K
CK
D000818:Animals; D001667:Binding, Competitive; D004268:DNA-Binding Proteins / Q000378:metabolism*; D020690:GTPase-Activating Proteins; D007328:Insulin / Q000378:metabolism; D007334:Insulin-Like Growth Factor I / Q000378:metabolism / Q000494:pharmacology*; D019869:Phosphatidylinositol 3-Kinases; D010750:Phosphoproteins / Q000378:metabolism*; D010766:Phosphorylation; D017853:Phosphotransferases (Alcohol Group Acceptor) / Q000378:metabolism*; D011233:Precipitin Tests; D011506:Proteins / Q000378:metabolism*; D016601:RNA-Binding Proteins / Q000378:metabolism*; D051381:Rats; D014407:Tumor Cells, Cultured / Q000187:drug effects / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D020703:ras GTPase-Activating Proteins
D004268:DNA-Binding Proteins; C489560:DOK1 protein, human; C074561:GAP-associated protein p62; D020690:GTPase-Activating Proteins; D007328:Insulin; D010750:Phosphoproteins; D011506:Proteins; D016601:RNA-Binding Proteins; D020703:ras GTPase-Activating Proteins; D014443:Tyrosine; D007334:Insulin-Like Growth Factor I; D019869:Phosphatidylinositol 3-Kinases; D017853:Phosphotransferases (Alcohol Group Acceptor)