Met Protein is an important component in the neurobiology of neurodegenerative diseases. This page provides detailed information about its structure, function, and role in disease processes.
MET (proto-oncogene, receptor tyrosine kinase) is the cell surface receptor for hepatocyte growth factor (HGF), also known as scatter factor. The HGF/MET signaling pathway is a major regulator of cell growth, motility, morphogenesis, and tissue repair. Upon HGF binding, MET undergoes dimerization and autophosphorylation, activating multiple downstream signaling cascades including RAS/RAF/MEK/ERK, PI3K/AKT, and STAT. In the developing brain, MET plays crucial roles in neuronal migration, axon guidance, and dendrite outgrowth. In adults, MET continues to be expressed in various brain regions and participates in synaptic plasticity, learning, and memory. Dysregulated MET signaling is implicated in cancer metastasis and has been linked to neurodegenerative diseases including Parkinson's disease, where altered HGF/MET signaling may affect dopaminergic neuron survival.
| MET Protein | |
|---|---|
| Protein Name | MET Protein |
| Gene | MET |
| UniProt ID | P08581 |
| PDB IDs | 1RPZ, 3L3V, 5HT5 |
| Molecular Weight | 139 kDa |
| Subcellular Location | Plasma membrane |
| Protein Family | MET/RTK family |
MET Protein is a MET/RTK family. This protein contains extracellular ligand-binding domains, a transmembrane helix, and an intracellular tyrosine kinase domain that is activated upon ligand binding and dimerization.
MET (c-Met) is the receptor tyrosine kinase for hepatocyte growth factor (HGF). HGF/MET signaling promotes cell scattering, proliferation, migration, and angiogenesis. MET is important for embryonic development, wound healing, and tissue regeneration. In the brain, MET/HGF signaling affects neuronal development, synaptic plasticity, and may have neuroprotective effects. MET is expressed in hippocampal neurons and regulates excitatory synaptic transmission.
MET is an oncogene frequently altered in cancer (amplification, mutations). MET dysregulation is found in AD and PD brains. HGF/MET signaling has neurotrophic and neuroprotective effects, making it a therapeutic target for neurodegeneration.
MET inhibitors are approved for cancer: Cabozantinib, Sunitinib, crizotinib. MET-targeted antibodies are in development. For neurodegeneration, HGF analogs and MET agonists are being explored for potential therapy.
The study of Met Protein has evolved significantly over the past decades. Research in this area has revealed important insights into the underlying mechanisms of neurodegeneration and continues to drive therapeutic development.
Historical context and key discoveries in this field have shaped our current understanding and will continue to guide future research directions.