Cell Signaling Technology

Product Pathways - Tyrosine Kinase/ Adaptors

Phospho-Met (Tyr1003) (13D11) Rabbit mAb #3135

Applications Reactivity MW (kDa) Source Isotype
W H M 145 Rabbit IgG

Applications Key:  W=Western Blotting
Reactivity Key:  H=Human  M=Mouse
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 (Tyr1003) (13D11) Rabbit mAb detects endogenous levels of Met only when phosphorylated at Tyr1003. This antibody may cross-react with other activated protein tyrosine kinases.

Source / Purification

Monoclonal antibodies are produced by immunizing rabbits with a synthetic phosphopeptide (KLH-coupled) corresponding to residues surrounding Tyr1003 of human Met.

Western Blotting

Western Blotting

Western blot analysis of extracts from A431 cells, untreated or HGF-treated using Phospho-Met (Tyr1003) (13D11) Rabbit mAb (upper and middle) and Met (25H2) Mouse mAb #3127 (lower). The middle blot was treated with CIP phosphatase before antibody probing.

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 cancers. 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.

Application References

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Companion Products

Rabbit Monoclonals Produced Using Epitomics® Technology, U.S. Patent No. 5,675,063.

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