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Signal transduction by tyrosine kinase growth factor receptors involves the activation of multiple intracellular signaling pathways. In many cases, this occurs via direct binding of a downstream signaling protein to the phosphorylated receptor via src-homology 2 domains on the signaling protein. In this review of the hepatocyte growth factor receptor c-met, the ability of the amino acid sequence of the receptor to dictate which signaling proteins are activated is described, with particular emphasis on association with the phosphatidylinositol 3-kinase. Recent developments that provide new understanding of the mechanisms of downstream signal transduction by the phosphatidylinositol 3-kinase are discussed, including how these might be involved in the mitogenic, motogenic, and tubulogenic effects of hepatocyte growth factor on renal epithelial cells.

Signal transduction by the hepatocyte growth factor receptor, c-met. Activation of the phosphatidylinositol 3-kinase.