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Signaling adapter that couples activated growth factor receptors to signaling pathway. Isoform p46Shc andisoform p52Shc, once phosphorylated, couple activated receptor tyrosine kinases to Ras via the recruitment of theGRB2/SOS complex and are implicated in the cytoplasmic propagation of mitogenic signals. Isoform p46Shc and isoformp52Shc may thus function as initiators of the Ras signaling cascade in various non-neuronal systems. Isoform p66Shcdoes not mediate Ras activation, but is involved in signal transduction pathways that regulate the cellular responseto oxidative stress and life span. Isoform p66Shc acts as a downstream target of the tumor suppressor p53 and isindispensable for the ability of stress-activated p53 to induce elevation of intracellular oxidants, cytochrome crelease and apoptosis. The expression of isoform p66Shc has been correlated with life span
