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Mechanism of RTK Signaling

Tyrosine kinase autophosphorylation is the major mechanism for recruiting downstream effectors, either through the binding of effectors to phosphotyrosine residues on the Tyr kinase polypeptide (Fig. 4-5) or through phosphorylation at Tyr of phosphotyrosine docking proteins—a phosphorylation that occurs consequent to Tyr kinase autophosphorylation-mediated activation. These docking proteins then themselves bind and recruit Tyr kinase effectors.

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IDENTIFICATION OF RTK TARGETS

Although the RTKs show vigorous phosphotransferase activity in vitro, the abundance of phosphotyrosine in intact cells is very low, and endogenous RTK substrates were hard to find. Even in RSV transformed cells, which contain a mutant, constitutively active retroviral tyrosine kinase transforming protein, the abundance of phosphotyrosine is less than 0.1% that of P-Ser plus P-Thr. In such cells, many of the proteins found to have P-Tyr proved to be abundant proteins (e.g., enolase or LDH) …