MET Gene: Function, Mutations, and Associated Diseases | Biomedical Resource

The MET gene encodes the hepatocyte growth factor receptor (HGFR), a receptor tyrosine kinase that binds hepatocyte growth factor (HGF). Upon ligand binding, MET dimerizes and autophosphorylates, activating downstream signaling pathways such as PI3K-AKT, RAS-MAPK, and STAT, which regulate cell proliferation, survival, motility, and morphogenesis. MET is essential for embryonic development and tissue regeneration, but aberrant activation (via mutation, amplification, or overexpression) contributes to oncogenesis and metastasis in various cancers.

Tissue Expression

Cell Line Expression

Hotspot Mutations

Mutation functional classification

• HGF/MET signaling pathway

• PI3K-AKT signaling pathway

• RAS-MAPK signaling pathway

• JAK-STAT signaling pathway

• Rap1 signaling pathway

• Regulation of actin cytoskeleton

The MET protein (UniProt P08581) is a single-pass type I membrane receptor tyrosine kinase. It is synthesized as a single-chain precursor that is cleaved into alpha and beta subunits linked by disulfide bonds. The extracellular domain contains Sema, PSI, and IPT domains; the intracellular domain contains a juxtamembrane region and a tyrosine kinase domain. Upon HGF binding, MET dimerizes and autophosphorylates key tyrosine residues (Y1234/Y1235 in the kinase domain, Y1349/Y1356 in the C-terminal docking site), recruiting adaptor proteins like GRB2, GAB1, and SHC to activate downstream pathways. MET is involved in embryogenesis, wound healing, and organ regeneration. Aberrant MET signaling is a therapeutic target in multiple cancers.