MET
Domain
The kinase domain is involved in SPSB1 binding.
The beta-propeller Sema domain mediates binding to HGF.
Function
Receptor tyrosine kinase that transduces signals from the extracellular matrix into the cytoplasm by binding to hepatocyte growth factor/HGF ligand. Regulates many physiological processes including proliferation, scattering, morphogenesis and survival. Ligand binding at the cell surface induces autophosphorylation of MET on its intracellular domain that provides docking sites for downstream signaling molecules. Following activation by ligand, interacts with the PI3-kinase subunit PIK3R1, PLCG1, SRC, GRB2, STAT3 or the adapter GAB1. Recruitment of these downstream effectors by MET leads to the activation of several signaling cascades including the RAS-ERK, PI3 kinase-AKT, or PLCgamma-PKC. The RAS-ERK activation is associated with the morphogenetic effects while PI3K/AKT coordinates prosurvival effects. During embryonic development, MET signaling plays a role in gastrulation, development and migration of muscles and neuronal precursors, angiogenesis and kidney formation. In adults, participates in wound healing as well as organ regeneration and tissue remodeling. Promotes also differentiation and proliferation of hematopoietic cells (By similarity).
(Microbial infection) Acts as a receptor for Listeria monocytogenes internalin InlB, mediating entry of the pathogen into cells.
Post-translational modifications
Autophosphorylated in response to ligand binding on Tyr-1235 and Tyr-1236 in the kinase domain leading to further phosphorylation of Tyr-1350 and Tyr-1357 in the C-terminal multifunctional docking site. Dephosphorylated by PTPRJ at Tyr-1350 and Tyr-1366. Dephosphorylated by PTPN1 and PTPN2 (By similarity).
Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation (By similarity).
(Microbial infection) Tyrosine phosphorylation is stimulated by L.monocytogenes InlB.
O-mannosylation of IPT/TIG domains by TMEM260 is required for protein maturation. O-mannosylated residues are composed of single mannose glycans that are not elongated or modified.
Sequence Similarities
Belongs to the protein kinase superfamily. Tyr protein kinase family.
Cellular localization
- Membrane
- Single-pass type I membrane protein
Alternative names
Hepatocyte growth factor receptor, HGF receptor, HGF/SF receptor, Proto-oncogene c-Met, Scatter factor receptor, Tyrosine-protein kinase Met, SF receptor, MET