SRC-3�G4 Mediates the Interaction of EGFR with FAK to Promote Cell Migration
Journal
Molecular Cell
Journal Volume
37
Journal Issue
3
Pages
321-332
Date Issued
2010
Author(s)
Long W.
Yi P.
Amazit L.
LaMarca H.L.
Ashcroft F.
Kumar R.
Mancini M.A.
Tsai S.Y.
O'Malley B.W.
Abstract
EGF induces signal transduction between EGFR and FAK, and FAK is required for EGF-induced cell migration. It is unknown, however, what factor mediates the interaction between EGFR and FAK and leads to EGF-induced FAK phosphorylation. Here, we identify SRC-3Delta4, a splicing isoform of the SRC-3 oncogene, as a signaling adaptor that links EGFR and FAK and promotes EGF-induced phosphorylations of FAK and c-Src. We identify three PAK1-mediated phosphorylations in SRC-3Delta4 that promote the localization of SRC-3Delta4 to the plasma membrane and mediate the interactions with EGFR and FAK. Importantly, overexpression of SRC-3Delta4 promotes MDA-MB231-induced breast tumor metastasis. Our findings identify phosphorylated SRC-3Delta4 as a missing adaptor between EGFR and its downstream signaling molecule FAK to coordinately regulate EGF-induced cell migration. Our study also reveals that a nuclear receptor coactivator can act in the periphery of a cell to directly mediate activation of an enzyme.
Type
journal article