Fig. 6.

Proposed mechanism for full ERK activation. Proposed mechanism for full ERK signaling includes SFK-independent activation through EGFR and Shc, whereas SFK is necessary for signaling from EGFR to PI3K. Amplified PI3K activity is responsible for driving Gab1 recruitment to the membrane via PIP₃. Gab1 phosphorylation creates a docking site for SHP2 to dephosphorylate RasGAP binding sites (blue star), potentially including Y373 on Gab1. Only combined activation through Shc and dephosphorylation of RasGAP binding sites through PI3K-Gab1-SHP2 result in full ERK activity.