A MAMMALIAN ADAPTER PROTEIN WITH CONSERVED SRC HOMOLOGY-2 AND PHOSPHOTYROSINE-BINDING DOMAINS IS RELATED TO SHC AND IS SPECIFICALLY EXPRESSED IN THE BRAIN

The Shc adaptor protein, hereafter referred to as ShcA, possesses two distinct phosphotyrosine-recognition modules, a C-terminal Src homolog y 2 (SH2) domain and an N-terminal phosphotyrosine-binding (PTB) domai n, and is itself phosphorylated on tyrosine In response to many extrac ellular signals, Phosphorylation of human ShcA at Tyr-317 within its c entral (CH1) region induces binding to the Grb2 SH2 domain and is ther eby implicated in activation of the Ras pathway, Two she-related genes (shcB and shcC) have been identified in the mouse, shcB is closely re lated to human SCK, while shcC has not yet been found In other organis ms, The ShcC protein is predicted to have a C-terminal SH2 domain, a C H1 region with a putative Grb2-binding site, and an N-terminal PTB dom ain, The ShcC and ShcB SH2 domains bind phosphotyrosine-containing pep tides and receptors with a specificity related to, but distinct from, that of the ShcA SH2 domain, The ShcC PTB domain specifically associat es in vitro with the autophosphorylated receptors for nerve growth fac tor and epidermal growth factor, These results indicate that ShcC has functional SH2 and PTB domains, In contrast to shcA, which is widely e xpressed, shcC RNA and proteins are predominantly expressed in the adu lt brain, These results suggest that ShcC may mediate signaling from t yrosine kinases in the nervous system, such as receptors for neurotrop hins.