GRAP is a GRB-2 like adaptor protein that is highly expressed in lymphoid tissues. It acts as a negative regulator of T cell receptor (TCR)-induced lymphocyte proliferation by downregulating the signaling to the Ras/ERK pathway []. It has been identified as a regulator of TGFbeta signaling in diabetic kidney tubules and may have a role in the pathogenesis of the disease []. GRAP contains an N-terminal SH3 domain, a central SH2 domain, and a C-terminal SH3 domain.
Growth factor receptor-bound protein 2 (Grb2) is an SH2 and SH3 domain-containing adaptor protein that links receptor tyrosine kinases to Ras signalling []. Grb2 interacts with the cytoplasmic tyrosine kinase ACK1 (activated Cdc42-associated kinase 1) and mediates its interaction with other receptor tyrosine kinases []. ACK1 is implicated in metastatic behaviour, cell spreading and migration, and epidermal growth factor receptor (EGFR) signalling [].Human GRAP and its Drosophila homologue, downstream of receptor kinase (drk), have been shown to have a function in hearing [].This entry includes a group of adapter proteins including Grb2, GRAP and GRAPL from humans. This entry also includes Sem-5 from Caenorhabditis elegans. Sem-5 is an adapter protein which modulates signaling mediated by several receptor tyrosine kinases such as egl-15 and let-23 probably acting upstream of let-60/ras [, ].
