|Human, mouse, rat|
Host Species and Isotype:
Met, a high affinity tyrosine kinase receptor for hepatocyte growth factor (HGF; also known as scatter factor), is a disulfide-linked heterodimer made of 45 kDa α- and 145 kDa β-subunits (Ref 1,2). The α-subunit and the amino-terminal region of the β-subunit form the extracellular domain. The remainder of the β-chain spans the plasma membrane and contains a cytoplasmic region with tyrosine kinase activity. Interaction of Met with HGF results in autophosphorylation at multiple tyrosines, which recruit several downstream signaling components, including Gab1, c-Cbl and PI3 kinase (Ref 3). These are fundamental events important to all of Met’s known biological functions. Addition of a phosphate at cytoplasmic Tyr1003 is essential for ubiquination and Met protein degradation (Ref 4). Phosphorylation of Tyr1234/1235 in the Met kinase domain is critical to kinase activation. Phosphorylation of Tyr1349 in the Met cytoplasmic domain provides a direct binding site for Gab1 (Ref 5). Altered Met levels and/or tyrosine kinase activities are found in several types of tumors, including renal, colon and breast cancers. Thus, Met is an attractive cancer therapeutic and diagnostic target (Ref 6).
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