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Hepatocyte growth factor regulates cell growth, cell motility, and morphogenesis by activating a tyrosine kinase signaling cascade after binding to the proto-oncogenic c-Met receptor. [ 6 ] [ 7 ] Hepatocyte growth factor is secreted by platelets , [ 8 ] and mesenchymal cells and acts as a multi-functional cytokine on cells of mainly epithelial ...
Hepatocyte growth factor receptor (HGF receptor) [5] [6] is a protein that in humans is encoded by the MET gene.The protein possesses tyrosine kinase activity. [7] The primary single chain precursor protein is post-translationally cleaved to produce the alpha and beta subunits, which are disulfide linked to form the mature receptor.
Human hepatocyte growth factor (HGF) is an 80kD [1] pleiotropic protein that is endogenously produced by a variety of cell types from the mesenchymal cell lineage (such as cardiomyocytes and neurons). [4] It is produced and proteolytically cleaved to its active state in response to cellular injury or during apoptosis.
Hepatocyte growth factor activator is a protein that in humans is encoded by the HGFAC gene. [5] [6] [7]The protein encoded by this gene, belongs to peptidase family S1. It is first synthesized as an inactive single-chain precursor before being activated to a heterodimeric form by endoproteolytic processing.
c-Met inhibitors are a class of small molecules that inhibit the enzymatic activity of the c-Met tyrosine kinase, the receptor of hepatocyte growth factor/scatter factor (HGF/SF). These inhibitors may have therapeutic application in the treatment of various types of cancers. [1] Many c-Met inhibitors are currently [when?] in clinical trials.
A growth factor is a naturally occurring substance capable of stimulating cell proliferation, wound healing, and occasionally cellular differentiation. [1] Usually it is a secreted protein or a steroid hormone .
Two such proteins that mediate the TGFβ pathway include SARA (the SMAD anchor for receptor activation) and HGS (Hepatocyte growth factor-regulated tyrosine kinase substrate). SARA is present in an early endosome which, by clathrin-mediated endocytosis, internalizes the receptor complex. [8] SARA recruits an R-SMAD.
Cabozantinib, which is an inhibitor of multiple tyrosine kinases including VEGFR, hepatocyte growth factor receptor (MET) and AXL and ramucirumab, an antibody directed against VEGF receptor 2, are second line therapies which have been shown to reduce the risk of death compared to placebo. [6] [79] [80]
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