A FAMILY OF SHC RELATED PROTEINS WITH CONSERVED PTB, CH1 AND SH2 REGIONS

Shc proteins are targets of activated tyrosine kinases and have been i mplicated in the transmission of activation signals to Ras. Upon phosp horylation, Shc proteins form stable complexes with cellular tyrosine- phosphorylated proteins and with the Grb2 adaptor protein, Two Shc iso forms of 52 and 46 kDa have been characterized. They share a C-termina l SH2 domain, a proline- and glycine-rich region (collagen homologous region 1; CH1) and a N-terminal phospho-tyrosine binding domain (PTB), We report here the initial characterization of two Shc related human cDNAs: ShcB and ShcC. The ShcB and ShcC cDNAs code for proteins that a re highly similar and share the same modular organization as Shc. PTB and SH2 domains of ShcB and ShcC have similar binding specificities in vitro and bind to activated EGFR in a phosphotyrosine-dependent manne r. Based on these findings we propose to rename Shc as ShcA. Anti-ShcB and anti-ShcC antibodies recognize specific polypeptides of 52, 47 kD a (ShcB) and 54 kDa (ShcC) in mammalian cells. Since these two genes a re predominantly expressed in specific brain tissues, these Shc family members may be involved in cell type-specific signaling, in the nervo us system.