Figure 2.

MET-HGF/SF signaling. The MET receptor is activated at the plasma membrane by binding of HGF/SF to the extracellular region of MET. Upon dimerization and activation, tyrosine phosphorylation occurs at Tyr1003 in the juxtamembrane CBL-binding site (shown in green), Tyr1230, Tyr1234, and Tyr1235 in the active site of the kinase (shown in light green), and Tyr1349 and Tyr1356 in the bidentate docking site (shown in pink). MET can then mediate several intracellular signaling pathways through a diverse array of adaptors and downstream effectors. The Gab1 and Grb2 adaptor proteins are critical mediators of MET activation and signaling through RAS-MAPK, PI3K-AKT, RAC1, and PAK pathways drive distinct cellular responses including proliferation, cell survival, and migration. (From Gherardi et al. 2006; reprinted, with permission, from Nature Publishing Group, © 2012.)