SHP2–EGFR States in Dephosphorylation Can Inform Selective SHP2 Inhibitors, Dampening RasGAP Action
Yonglan Liu,
Hyunbum Jang,
Ruth Nussinov
Abstract:SHP2 is a positive regulator of the EGFR-dependent Ras/MAPK
pathway.
It dephosphorylates a regulatory phosphorylation site in EGFR that
serves as the binding site to RasGAP (RASA1 or p120RasGAP). RASA1
is activated by binding to the EGFR phosphate group. Active RASA1
deactivates Ras by hydrolyzing Ras-bound GTP to GDP. Thus, SHP2 dephosphorylation
of EGFR effectively prevents RASA1-mediated deactivation of Ras, thereby
stimulating proliferation. Despite knowledge of this vital regulation
in cell life, mechanis… Show more
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