Signaling via Shc family adapter proteins

The adapter protein She was initially identified as an SH2 containing proto-oncogene involved in growth factor signaling. Since then a number of studies in multiple systems have implicated a role for She in signaling via many different types of receptors, such as growth factor receptors, antigen receptors, cytokine receptors, G-protein coupled receptors, hormone receptors and integrins. In addition to the ubiquitous ShcA, two other she gene products, ShcB and ShcC, which are predominantly expressed in neuronal cells, have also been identified. ShcA knockout mice are embryonic lethal and have clearly suggested an important role for ShcA in vivo. Based on dominant negative studies and mouse embryos deficient in ShcA, a clear role for She in leading to mitogen activated protein kinase (MAPK) activation has been established. However MAPK activation may not be the sole function of She proteins. Although She has also been linked to other signaling events such as c-Myc activation and cell survival, the mechanistic understanding of these signaling events remains poorly characterized. Given the apparently central role that She plays signaling via many receptors, delineating the precise mechanism(s) of She-mediated signaling may be critical to our understanding of the effects mediated through these receptors.