The MET gene (MET Proto-Oncogene, Receptor Tyrosine Kinase) encodes the hepatocyte growth factor receptor (HGFR), a receptor tyrosine kinase that plays crucial roles in cell growth, survival, migration, and tissue morphogenesis. In the nervous system, MET signaling is important for neuronal development, migration, and synaptic plasticity, and is implicated in neurodegenerative diseases and brain cancers.
| Attribute |
Value |
| Symbol |
MET |
| Full Name |
MET Proto-Oncogene, Receptor Tyrosine Kinase |
| Chromosomal Location |
7q31.2 |
| NCBI Gene ID |
4233 |
| OMIM ID |
164860 |
| Ensembl ID |
ENSG00000105976 |
| UniProt ID |
P08581 |
| Protein Size |
1390 amino acids |
| Molecular Weight |
~140 kDa (precursor), ~170 kDa (mature) |
MET is a heterodimeric receptor:
- α-subunit ( extracellular): Ligand binding
- β-subunit (transmembrane): Contains tyrosine kinase domain
- Semaphorin (Sema) domain: HGF binding
- Tyrosine Kinase Domain: Catalytic activity (Y1234, Y1235)
- C-terminal Docking Sites: Multiple tyrosine residues for signaling
- Neuronal Migration: Critical for cortical neuron migration
- Axon Guidance: Directs axon growth cones
- Dendritic Arborization: Promotes dendrite outgrowth
- Synapse Formation: Regulates synaptic development
¶ Plasticity and Repair
- Synaptic Plasticity: Involved in learning and memory
- Neurogenesis: Regulates neural stem cell function
- Axon Regeneration: Promotes regeneration after injury
- Astrocyte Development: Important for astrocyte maturation
- Glial Support: Supports neuronal survival
MET is expressed in various tissues:
- Brain: Neurons, astrocytes, neural progenitor cells
- Liver, kidney, muscle
- Endothelial cells
- Epithelial cells
In the brain, MET expression is highest during development and decreases in adulthood.
- Synaptic Dysfunction: Altered MET signaling in AD brain
- Aβ Interaction: Amyloid-beta affects MET signaling
- Cognitive Decline: Linked to memory deficits
- Dopaminergic Neurons: MET in substantia nigra
- Neuroprotection: HGF/MET signaling is neuroprotective
- Therapeutic Potential: MET agonists being explored
- Oncogenic Role: MET amplification in glioblastoma
- Invasion: Promotes tumor cell invasion
- Therapeutic Target: MET inhibitors in clinical trials
- Genetic Associations: MET variants linked to ASD risk
- Synaptic Function: Altered cortical connectivity
MET activates multiple downstream pathways:
| Pathway |
Function |
| PI3K/AKT |
Cell survival, growth |
| MAPK/ERK |
Proliferation, differentiation |
| STAT |
Transcription regulation |
| PLCγ |
Calcium signaling |
| Drug |
Mechanism |
Status |
| Crizotinib |
MET inhibitor |
FDA-approved for NSCLC |
| Cabozantinib |
Multi-kinase inhibitor |
FDA-approved |
| Tepotinib |
Selective MET inhibitor |
FDA-approved |
| AMG 208 |
MET inhibitor |
Clinical trials |