Shc

Shc is a prototype adapter protein that is expressed from the earliest stages of T-cell development. Shc becomes rapidly tyrosine phosphorylated after T-cell receptor (TCR) engagement. Three shc genes have been identified in mammals and their gene products have been referred to as ShcA, ShcB and ShcC. ShcA is ubiquitously expressed, while shcB and ShcC expression appear limited to neuronal cells. ShcA is expressed as three isoforms of about 46, 52 and 66 kDa. Shc is composed of an N-terminal PTB, a central collagen-homology (CH) domain and a C-terminal SH2 domain. The 66 kDa isoform of ShcA is expressed in most cells except in the hematopoietic lineage and contains an additional amino-terminal CH-like region. The tyrosine phosphorylation of Shc has been noticed upon engagement of numerous cell surface receptors such as growth factor receptors, antigen receptors, cytokine receptors, G-protein coupled receptors and hormone receptors. The involvement of ShcA in the Ras signaling pathway is initiated by the tyrosinephospho­rylation of the receptor protein tyrosine kinases (RPTKs) and subsequent interaction with Grb2 and Ras guanine nucleotide exchange factor, Sos. The Shc : Grb2 : Sos complex gets localized to the membrane through the interaction of Shc with the phosphorylated receptor. Membrane-bound Sos then activates Ras by catalysing GDP/GTD exchange. GTPbound Ras then triggers downstream events, which include Raf, the mitogen-activated protein kinases (MAPKs) and MAPK kinase (MEK).