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Signals from most growth factors and cytokines are transduced by receptor tyrosine kinases or non-receptor tyrosine kinases. Activated tyrosine kinases phosphorylate their substrates, which mediate the cellular response to extracellular stimuli. A long-sought major substrate termed p62dok (downstream of tyrosine kinase) for many tyrosine kinases including c-kit, v-abl, v-Fps, v-Src, v-Fms, and activated EGF, PDGF, IGF, VEGF and insulin receptors was identified recently from human and mouse by several laboratories. Upon phosphorylation, p62dok forms a complex with the ras GTPase-activating protein (RasGAP). p62dok represents a new family with very recently identified p56dok.