Synthetic phosphopeptide corresponding to residues surrounding Tyr490 of human TrkA. Species sequence homology: mouse.
The family of Trk receptor tyrosine kinases consists of TrkA, TrkB and TrkC. While the sequence of these family members is highly conserved, these family members are activated by different neurotrophins: TrkA by NGF, TrkB by BDNF or NT4 and TrkC by NT3. TrkA regulates proliferation and is important for development and maturation of the nervous system (1). Phosphorylation at Tyr490 is required for Shc association and activation of the Ras-MAP kinase cascade. Residues Tyr674/675 lie within the catalytic domain, and phosphorylation at this site reflects TrkA kinase activity (2-6). Point mutations, deletions and chromosomal rearrangements chimera) cause ligand-independent receptor dimerization and activation of TrkA. Many malignancies (breast, colon, prostate and thyroid carcinomas and acute myeloid leukemia) have activated TrkA. Expression of TrkA in neuroblastomas is a good prognostic marker because it signals growth arrest and differentiation of cells originating from the neural crest (1). The phosphorylation sites are conserved between TrkA and TrkB: Tyr490 of TrkA corresponds to Tyr512 in TrkB, and Tyr674/675 of TrkA to Tyr706/707 in TrkB of the human sequence (7). TrkB is overexpressed in tumors such as neuroblastoma, prostate adenocarcinoma and pancreatic ductal adenocarcinoma. In neuroblastomas overexpression of TrkB correlates with unfavorable disease outcome when autocrine loops signaling tumor survival are potentiated by additional overexpression of brain-derived neurotrophic factor BDNF). An alternatively spliced truncated TrkB isoform lacking the kinase domain is overexpressed in Wilmss tumors and this isoform may act as a dominant-negative to TrkB signaling (8). Applications: Suitable for use in Western Blot and Immunoprecipitation. Other applications not tested. Recommended Dilution: Western Blot: 1:1000. For Western blot, incubate membrane with diluted antibody in 5% w/v BSA, 1X TBS, 0.1% Tween-20 at 4C with gentle shaking overnight. Immunoprecipitation: 1:50 Optimal dilutions to be determined by the researcher. Storage and Stability: May be stored at 4C for short-term only. For long-term storage, aliquot and store at -20C. Aliquots are stable for 12 months at -20C. For maximum recovery of product, centrifuge the original vial after thawing and prior to removing the cap. Further dilutions can be made in assay buffer.
