MET receptor tyrosine kinase (MET)

MET receptor tyrosine kinase is a transmembrane protein encoded by the MET proto-oncogene. It is produced as a precursor that is cleaved into an extracellular α-subunit and a transmembrane β-subunit linked by disulfide bonds. The extracellular portion contains Sema, PSI, and Ig domains, while the intracellular portion includes a juxtamembrane segment, a tyrosine kinase domain, and a C-terminal tail. MET is activated by its ligand, hepatocyte growth factor (HGF), leading to dimerization, autophosphorylation, and recruitment of adaptor proteins. This triggers downstream signaling pathways such as RAS/MAPK, PI3K/AKT, and STAT3, which regulate cellular functions like proliferation, scattering, invasion, survival, and angiogenesis. MET expression is regulated transcriptionally and negatively by phosphatases and ubiquitination. Deregulation of MET through overexpression, activating mutations, or gene amplification contributes significantly to cancer development and progression in various tumor types, including renal carcinomas, head and neck cancer, and glioblastomas. Due to its critical role in cancer, MET is considered a promising therapeutic target, and several inhibitors have been developed to block its activity.

Other names

c-MetMET proto-oncogeneHGF receptor

Drugs targeting MET typically act as tyrosine kinase inhibitors that disrupt MET signaling, thereby inhibiting tumor growth, progression, metastasis, and therapeutic resistance.