Tyrosine-protein kinase Met receptor (MET or c-MET)

Tyrosine-protein kinase Met receptor (MET) is a single-pass transmembrane receptor tyrosine kinase encoded by the MET proto-oncogene. It is initially synthesized as a precursor and cleaved into extracellular α (50 kDa) and transmembrane β (140 kDa) chains linked by disulfide bonds[1][5][11][12][14]. The extracellular portion contains a SEMA domain (for ligand binding), a PSI domain, and four immunoglobulin-plexin-transcription (IPT) repeats, followed by a transmembrane region. The intracellular segment includes a juxtamembrane domain, a tyrosine kinase domain, and a C-terminal docking tail. The MET receptor binds hepatocyte growth factor (HGF), leading to dimerization and autophosphorylation at critical tyrosines (Tyr1234, Tyr1235, Tyr1349, Tyr1356), recruiting signaling molecules such as GRB2, GAB1, PI3K, and SRC family kinases[4][5][11][12][14]. Activated MET drives cellular responses including proliferation, motility, survival, angiogenesis, and morphogenesis. Aberrations of MET (overexpression, mutations, amplification) are key drivers in several cancers, making MET a major target for small-molecule and antibody therapeutics[3][7][9][12].

Other names

c-METHepatocyte growth factor receptorMET proto-oncogene, receptor tyrosine kinaseHGFR

Kinase inhibition (most drugs block the ATP binding site of the intracellular tyrosine kinase domain, preventing phosphorylation and downstream signaling). Downregulation of receptor function (e.g., promoting receptor degradation). Interfering with ligand-receptor interaction, primarily inhibiting HGF-induced MET activation.