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By Margaret A. Shupnik

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Faux MC, Scott JD. Molecular glue: kinase anchoring and scaffold proteins. Cell 1996; 85:9–12. 38 Quon and Taylor 123. Liu P, Ying Y-S, Anderson RGW. Platelet-derived growth factor activates mitogen-activated protein kinase in isolated caveolae. Proc Natl Acad Sci USA 1997; 94:13,666–13,670. 124. Couet J, Sargiacomo M, Lisanti MP. Interaction of a receptor tyrosine kinase, EGF-R, with caveolins: caveolin binding negatively regulates tyrosine and serine/threonine kinase activities. J Biol Chem 1997; 272:30,429–30,438.

SH3 domains bind with high affinity to particular proline-rich sequences (4). , IRS-1). , GRB-2, Nck, and the p85 regulatory subunit of PI3K) are known as adaptor proteins because they have no intrinsic catalytic activity and their function involves forming specific signaling complexes mediated by the simultaneous interactions of multiple SH2/SH3 domains on the adaptor protein with both upstream and downstream signaling molecules. Activation of Ras and PI3K, two major effector pathways common to a number of growth factor receptors including the insulin receptor, fit this latter pattern.

Insulin-stimulated GLUT4 translocation is mediated by a divergent intracellular signaling pathway. J Biol Chem 1995; 270:27,991–27,994. Hausdorff SF, Frangioni JV, Birnbaum MJ. Role of p21ras in insulin-stimulated glucose transport in 3T3-L1 adipocytes. J Biol Chem 1994; 269:21,391–21,394. Fingar DC, Birnbaum MJ. A role for Raf-1 in the divergent signaling pathways mediating insulinstimulated glucose transport. J Biol Chem 1994; 269:10,127–10,132. Kohn AD, Summers SA, Birnbaum MJ, Roth RA. Expression of a constitutively active Akt Ser/Thr kinase in 3T3-L1 adipocytes stimulates glucose uptake and glucose transporter 4 translocation.

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