Cell Signaling Technology

Product Pathways - Tyrosine Kinase/ Adaptors

Phospho-Met (Tyr1349) Antibody #3121

Applications Reactivity MW (kDa) Source
W IP H M R 145 Rabbit

Applications Key:  W=Western Blotting  IP=Immunoprecipitation
Reactivity Key:  H=Human  M=Mouse  R=Rat
Species enclosed in parentheses are predicted to react based on 100% sequence homology. Species cross-reactivity is determined by Western blot.

Specificity / Sensitivity

Phospho-Met (Tyr1349) Antibody detects endogenous levels of Met only when phosphorylated at tyrosine 1349. This antibody may cross-react with activated EGF, PDGF, insulin and FGF receptors.

Source / Purification

Polyclonal antibodies are produced by immunizing rabbits with a synthetic phospho-peptide (KLH-coupled) corresponding to residues surrounding Tyr1349 of human Met. Antibodies are purified by protein A and peptide affinity chromatography.phy.

Western Blotting

Western Blotting

Western blot analysis of extracts from mIMCD-3 cells, untreated or HGF-stimulated (40 ng/ml for 2 minutes), using Phospho-Met (Tyr1349) Antibody (upper) or Met antibody (lower).

Western Blotting

Western Blotting

Western blot analysis of extracts from Vero cells, treated with In1B (3 nM) for the indicated times, using Phospho-Met (Tyr1349) Antibody (upper) or Met antibody (lower). In1B is a c-Met activator (Shen, Y. et al. 2000, Cell 103, 501-510). (In1B provided by Dr. K. Ireton, University of Toronto, Canada.)

Background

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 (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 (3). These fundamental events are important for all of the biological functions involving Met kinase activity. Addition of a phosphate at cytoplasmic Tyr1003 is essential for ubiquitination and Met protein degradation (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 (5). Altered Met levels and/or tyrosine kinase activities are found in several types of tumors, including renal, colon and breast. Thus, Met is an attractive cancer therapeutic and diagnostic target (6).

  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.

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