Research ArticleEGFR Signaling

EGFR-activated Src family kinases maintain GAB1-SHP2 complexes distal from EGFR

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Science Signaling  12 May 2015:
Vol. 8, Issue 376, pp. ra46
DOI: 10.1126/scisignal.2005697

Remote control signaling

The receptor tyrosine kinase EGFR promotes cell proliferation in response to ligand activation. One of the downstream responses to EGF binding to EGFR is the tyrosine phosphorylation of the adaptor GAB1, which associates with and activates the phosphatase SHP2. Furcht et al. found that Src family kinases counteracted GAB1 dephosphorylation, which disrupts the GAB1-SHP2 interaction and attenuates EGFR signaling. This pathway enabled GAB1 to remain in association with SHP2 and stay phosphorylated longer than EGFR was activated by EGF. Furthermore, the active GAB1-SHP2 complexes persisted in the cytosol away from the activated EGFR. Computational modeling indicated a requirement for a time delay between EGFR inactivation and that of Src family kinases to enable protracted GAB1-SHP2 persistence.

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