Phospho-Met rabbit polyclonal antibody recognizes human, mouse, and rat Met phosphorylated at tyrosine 1003 in western blot.
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).

References:

1. Weidner, K.M. et al. (1993) J. Cell Biol. 121, 145-154.
2. Park, M. et al. (1986) Cell 45, 895-904.
3. Bardelli, A. et al. (1997) Oncogene 15, 3103-3111.
4. Taher, T.E. et al. (2002) J. Immunol. 169, 3793-3800.
5. Schaeper, U. et al. (2000) J. Cell Biol. 149, 1419-1432.
6. Traxler, P. et al. (2001) Med. Res. Rev. 21, 499-512.