The ShcD signaling adaptor facilitates ligand-independent phosphorylation of the EGF receptor.

ABSTRACT: Proto-oncogenic Src homology and collagen (Shc) proteins have been considered archetypal adaptors of epidermal growth factor receptor (EGFR)-mediated signaling. We report that in addition to its role as an EGFR-binding partner and Grb2 platform, ShcD acts noncanonically to promote phosphorylation of select EGFR residues. Unexpectedly, Y1068, Y1148, and Y1173 are subject to ShcD-induced, cell-autonomous hyperphosphorylation in the absence of external stimuli. This response is not elicited by other Shc proteins and requires the intrinsic EGFR kinase, as well as the ShcD phosphotyrosine-binding (PTB) domain. Assessments of Erk, Akt, phospholipase C 1γ, and FAK pathways reveal no apparent distal signaling targets of ShcD. Nevertheless, the capacity of cultured cells to repopulate a wounded mon

SUBMITTER: Wills MK 

PROVIDER: S-EPMC3952845 | biostudies-literature | 2014 Mar

REPOSITORIES: biostudies-literature