Emerging roles for SH2/PTB-containing Shc adaptor proteins in the developing mammalian brain

In mammalian systems, SH2-containing cytoplasmic signalling molecules are known to play an important role in determining cell responsiveness to the environment. In particular, following activation of a receptor protein tyrosine kinase (RPTK), proteins like Shc and Grb2 bind to phosphotyrosine residues of stimulated receptors, thereby activating downstream components of specific signalling pathways. The ShcA gene was identified in 1992 and was found to encode three proteins with properties of adaptor molecules coupling RPTKs to Ras. Early data obtained in non-neuronal cells have revealed that Shc and Grb2 proteins are highly expressed and activated in all cells. However, recent analyses of ShcA mRNA and protein in the developing brain revealed progressive downregulation of their expression during differentiation from neuroblasts to neurons. Conversely, the two newly identified Shc homologues (ShcB/Sli and ShcC/Rai) are highly expressed in the mature brain.Thus, variations in the intracellular levels of adaptor proteins might represent one of the mechanisms by which a differentiating cell changes its ability to respond to a given factor, allowing a cell to choose between proliferation and differentiation.