The SH2-containing Shc adapter proteins are targets of activated tyrosine kinases and are implicated in the transmission of activation signals to the Ras/mitogen-activated protein kinase (MAPK) pathway []. Three Shc genes were originally identified in mammals that encode proteins characterised by an amino-terminal phosphotyrosine binding (PTB) domain and a carboxy-terminal Src homology 2 domain. Shc1 (ShcA) is ubiquitously expressed, whereas expression of Shc2 (ShcB) and Shc3 (ShcC) appears to be limited to neuronal cells [].A fourth Shc family protein, ShcD/Shc4, is expressed in adult brain and skeletal muscle. ShcD can associate via its PTB domain with the phosphorylated muscle-specific kinase (MuSK) receptor tyrosine kinase and undergo tyrosine phosphorylation downstream of activated MuSK. Therefore, ShcD may mediate a specific aspect of signalling downstream of the MuSK receptor []. ShcD also interacts with EGFR receptor (epidermal growth factor receptor) and facilitates its ligand-independent phosphorylation []. ShcD has been shown to be a modulator in the transition of embryonic stem cell (ESC) to epiblast stem cells (EpiSCs), the initial step for ESCs to commit to differentiation [].
