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Interaction between the p21ras GTPase activating protein and the insulin receptor.

1992; Elsevier BV; Volume: 267; Issue: 33 Linguagem: Inglês

10.1016/s0021-9258(18)35945-3

1083-351X

Gijsbertus J. Pronk, René H. Medema, Boudewijn Burgering, R Clark, Frank McCormick, Johannes L. Bos,

Cancer-related Molecular Pathways

We investigated the involvement of the ~21'"-GTPase activating protein (GAP) in insulin-induced signal transduction.In cells overexpressing the insulin receptor, we did not observe association between GAP and the insulin receptor after insulin treatment nor the phosphorylation of GAP on tyrosine residues.However, after insulin treatment in the presence of the phosphotyrosine phosphatase inhibitor phenylarsine oxide (PAO), 5-10% of GAP was found to be associated with the insulin receptor, and, in addition, a fraction of total GAP was phosphorylated on tyrosine, Using in vitro binding we showed that the N-terminal part of GAP containing the src-homology domains 2 and 3 (SH2-SH3-SH2 region) is involved in binding to the autophosphorylated insulin receptor &chain.In vitro binding between GAP and the autophosphorylated insulin receptor occurred independently of PA0 pretreatment.These results suggest that GAP can transiently interact with the insulin receptor after insulin treatment, and this interaction is arrested after PA0 pretreatment.p21" is a small guanine nucleotide-binding protein which is involved in a number of growth factor-stimulated signal transduction pathways (Hall, 1990).Signaling through p21" appears to be, at least in part, regulated by the p21r"-GTPase activating protein (GAP).'GAP is involved in controlling the level of active GTP-bound p21" and may be functioning as a downstream target of p21" as well (Adari et al.,