Fig. 1
From: Molecular mechanism(s) of regulation(s) of c-MET/HGF signaling in head and neck cancer
Different downstream signaling pathways activated through c-MET and its interactive other membrane receptors. HGF released through tumor associated fibroblast cells in microenvironment binds to c-MET and activates it through autophosphorylation of tyrosines Y1234 and Y1235 within the activation loop of the kinase domain and subsequent phosphorylation of tyrosines Y1349 and Y1356 near the -COOH terminus. Major adapter proteins and direct kinase substrates activated downstream in the c-MET pathway include growth factor receptor-bound protein 2 (GRB2), Grb2-associated adaptor protein 1 (GAB1), phosphatidylinositol 3-kinase (PI3K), son of sevenless (SOS), rat sarcoma oncogene homolog (RAS), mitogen-activated protein kinase (MAPK), signal transducer and activator of transcription 3/5 (STAT 3/5), SRC, SRC homology protein tyrosine phosphatase 2 (SHP2), SRC homology domain c-terminal adaptor homolog (SHC), phospholipase c-γ (PLC), Ras-related C3 botulinum toxin substrate 1 (RAC1), p21-activated kinase (PAK), focal adhesion kinase (FAK), AKT, and mammalian target of rapamycin (mTOR). Crosstalk between c-MET and various membrane protein partners, including the epidermal growth factor receptor (EGFR), the plexin B family, α6β4 integrin, and CD44, results in additional signaling response modulation