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Rabbit Anti-Phospho-Met (Tyr1234 + Tyr1235)/FITC Conjugated antibody
background:
c-Met, a member of the tyrosine kinase superfamily, is the receptor for hepatocyte growth factor, also known as scatter factor (HGF/SF). The mature c-Met protein is a disulfide-linked heterodimer with Mr=190 kDa composed of a heavily glycosylated alpha subunit that is completely extracellular in localization, and a beta subunit comprising an extracellular ligand binding domain, a single transmembrane domain, and a cytoplasmic tyrosine kinase domain. Cells expressing c-Met include epithelial cells, endothelial cells, blood cells of various types, and glomerular mesenchymal cells.
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.
Acts as a receptor for Listeria internalin inlB, mediating entry of the pathogen into cells.
Subunit:
Heterodimer made of an alpha chain (50 kDa) and a beta chain (145 kDa) which are disulfide linked. Binds PLXNB1. Interacts when phosphorylated with downstream effectors including STAT3, PIK3R1, SRC, PCLG1, GRB2 and GAB1. Interacts with SPSB1, SPSB2 and SPSB4 (By similarity). Interacts with INPP5D/SHIP1. When phosphorylated at Tyr-1356, interacts with INPPL1/SHIP2. Interacts with RANBP9 and RANBP10, as well as SPSB1, SPSB2, SPSB3 and SPSB4. SPSB1 binding occurs in the presence and in the absence of HGF, however HGF treatment has a positive effect on this interaction. Interacts with MUC20; prevents interaction with GRB2 and suppresses hepatocyte growth factor-induced cell proliferation. Interacts with GRB10.
Subcellular Location:
Membrane; Single-pass type I membrane protein.
Isoform 3: Secreted.
Tissue Specificity:
Expressed in normal hepatocytes as well as in epithelial cells lining the stomach, the small and the large intestine. Found also in basal keratinocytes of esophagus and skin. High levels are found in liver, gastrointestinal tract, thyroid and kidney. Also present in the brain.
Post-translational modifications:
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 SLCterminal multifunctional docking site.
Dephosphorylated by PTPRJ at Tyr-1349 and Tyr-1365.
Ubiquitinated. Ubiquitination by CBL regulates the receptor stability and activity through proteasomal degradation.
DISEASE:
Note=Activation of MET after rearrangement with the TPR gene produces an oncogenic protein.
Note=Defects in MET may be associated with gastric cancer.
Hepatocellular carcinoma (HCC) [MIM:114550]: A primary malignant neoplasm of epithelial liver cells. The major risk factors for HCC are chronic hepatitis B virus (HBV) infection, chronic hepatitis C virus (HCV) infection, prolonged dietary aflatoxin exposure, alcoholic cirrhosis, and cirrhosis due to other causes. Note=The disease is caused by mutations affecting the gene represented in this entry.
Renal cell carcinoma papillary (RCCP) [MIM:605074]: A subtype of renal cell carcinoma tending to show a tubulo-papillary architecture formed by numerous, irregular, finger-like projections of connective tissue. Renal cell carcinoma is a heterogeneous group of sporadic or hereditary carcinoma derived from cells of the proximal renal tubular epithelium. Note=The disease is caused by mutations affecting the gene represented in this entry.
Note=A common allele in the promoter region of the MET shows genetic association with susceptibility to autism in some families. Functional assays indicate a decrease in MET promoter activity and altered binding of specific transcription factor complexes.
Note=MET activating mutations may be involved in the development of a highly malignant, metastatic syndrome known as cancer of unknown primary origin (CUP) or primary occult malignancy. Systemic neoplastic spread is generally a late event in cancer progression. However, in some instances, distant dissemination arises at a very early stage, so that metastases reach clinical relevance before primary lesions. Sometimes, the primary lesions cannot be identified in spite of the progresses in the diagnosis of malignancies.
Similarity:
Belongs to the protein kinase superfamily. Tyr protein kinase family.
Contains 3 IPT/TIG domains.
Contains 1 protein kinase domain.
Contains 1 Sema domain.
Database links:
Entrez Gene: 4233 Human
Entrez Gene: 17295 Mouse
Entrez Gene: 24553 Rat
Omim: 164860 Human
SwissProt: P08581 Human
SwissProt: P16056 Mouse
SwissProt: P97523 Rat
Unigene: 132966 Human
Unigene: 86844 Mouse
Unigene: 10617 Rat
Important Note:
This product as supplied is intended for research use only, not for use in human, therapeutic or diagnostic applications.
细胞膜受体（Membrane Receptors)
c-Met蛋白是肝细胞生长因子受体（Hepatocyte growth factor receptor, HGFR），又称受体蛋白酪氨酸激酶，肝细胞生长因子和过度表达的c-Met(HGFR)蛋白结合，在肿瘤的发生、进展和血管形成中都起着重要作用。
c-met蛋白也是HGF特异性受体，具有内源性酪氨酸激酶的活性，HGF与c-met蛋白特异性结合对肿瘤细胞生长、分化及恶性转化可能具有重要的关联。
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