||Purified polyclonal phospho-Met antibody specific for Human c-Met for use in Western Blot.
Met is a proto-oncogenic receptor tyrosine kinase with high affinity for hepatocyte growth factor. The primary single chain precursor protein is post-translationally cleaved to produce the 45 kDa alpha- and 145 kDa beta-subunits, which are disulfide linked to form the mature receptor. Ligand-binding induces autophosphorylation at multiple tyrosines, which recruit several downstream signaling components, including Gab1, c-Cbl and PI3 kinase. Activating point mutations cause hereditary papillary renal carcinoma. Mutations also seen in sporadic renal cell carcinoma and childhood hepatocellular carcinoma. Upregulation in carcinomas and sarcomas correlates with metastasis and poor outcome. Some gastric carcinomas harbor a translocation that creates an activated TPR-Met fusion protein. A small molecule inhibitor (PHA-665752) shows an effect in gastric carcinoma xenografts.
||MET is a member of the Tyr protein kinase family and is normally expressed by epithelial cells. However, MET is also found on endothelial cells, neurons, hepatocytes, hematopoietic cells, and melanocytes. HGF expression is restricted to cells of mesenchymal origin. MET is a single-pass type I membrane protein found in the cell membrane of most mammalian cells.
|Implications in Disease
||MET pathway plays an important role in the development of cancer through activation of key oncogenic pathways (RAS, PI3K, STAT3, beta-catenin), angiogenesis (sprouting of new blood vessels from pre-existing ones to supply a tumor with nutrients) and “Scatter” (cells dissociation due to metalloprotease production), which often leads to metastasis. Coordinated down-regulation of both MET and its downstream effector extracellular signal-regulated kinase 2 (ERK2) by miR-199a may be effective in inhibiting not only cell proliferation but also motility and invasive capabilities of tumor cells. MET amplification has also emerged as a potential biomarker of the clear cell tumor subtype. The amplification of the cell surface receptor MET drives resistance to anti-EGFR therapies in colorectal cancer. The SFARIgene database lists MET with an autism score of 2.0, which indicates that it is a strong candidate for playing a role in cases of autism. The database also identifies at least one study that found a role for MET in cases of schizophrenia.
||MET contains 1390 amino acids and has a molecular weight of 155541 Da. It is composed of a kinase domain involved in SPSB1 binding, a beta-propeller Sema domain which mediates binding to HGF and 3 IPT/TIG domains.
||MET is autophosphorylated in response to ligand binding on Tyr-1234 and Tyr-1235 in the kinase domain leading to further phosphorylation of Tyr-1349 and Tyr-1356 in the C-terminal multifunctional docking site. It is dephosphorylated by PTPRJ at Tyr-1349 and Tyr-1365. Dephosphorylated by PTPN1 and PTPN21. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation. Glycosylation occurs at Asn45, Asn106, Asn149, Asn202, Asn399, Asn405, Asn607, Asn635, Asn785, Asn879 and Asn930.
||Entrez Gene: 4233 Human, Omim: 164860 Human, SwissProt: P08581 Human, Unigene: 132966 Human