Gab1:Grb2 binds to EGF:Phospho-EGFR Gab1 binds phosphatidylinositol-3,4,5-trisphosphate Activation of SHP2 through the binding to phospho-Gab1 Gab1 phosphorylation by EGFR kinase SHP2 dephosphorylates Tyr 992 on EGFR Dephosphorylation of Gab1 by SHP2 Sustained activation of SRC kinase by SHP2 Dephosphorylation of PAG by SHP2 PIK3 converts phosphatidylinositol-4,5-bisphosphate (PIP2) to phosphatidylinositol-3,4,5-trisphosphate (PIP3) PIK3 catalytic subunit binds to EGF:EGFR:GRB2:GAB1:PIK3R1 GRB2:GAB1:PIK3R1 binds to phosphorylated EGFR Binding of PIK3 regulatory alpha subunit to GRB2:GAB1 Binding of GRB2 to GAB1 PIP3 activates AKT signaling GAB1 signalosome Authored: Castagnoli, L, 2006-10-10 13:09:34 GAB1 is recruited to the activated EGFR indirectly, through GRB2. GAB1 acts as an adaptor protein that enables formation of an active PIK3, through recruitment of PIK3 regulatory subunit PIK3R1 (also known as PI3Kp85), which subsequently recruits PIK3 catalytic subunit PIK3CA (also known as PI3Kp110). PIK3, in complex with EGFR, GRB2 and GAB1, catalyzes phosphorylation of PIP2 and its conversion to PIP3, which leads to the activation of the AKT signaling. Pubmed15550174 Reactome Database ID Release 43180292 Reactome, http://www.reactome.org ReactomeREACT_12578 Reviewed: Heldin, CH, 2008-02-12 09:44:02 PathwayStep3903 PathwayStep3904 PathwayStep3905 PathwayStep3900 PathwayStep3901 PathwayStep3902 PathwayStep3899 PathwayStep3897 PathwayStep3898 PathwayStep3868 PathwayStep3867 PathwayStep3866 PathwayStep3865 PathwayStep3864