Phospho-TrkA (Tyr674/675)/TrkB (Tyr706/707) (C50F3) Rabbit mAb

• 产品编号：CST-4621S      品牌：CST       原厂货号：4621S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-TrkA (Tyr674/675)/TrkB (Tyr706/707) (C50F3)Rabbit mAb 兔单抗可分别识别内源性的Tyr674/675磷酸化的TrkA和Tyr706/707磷酸化的TrkB。此抗体可能与某大约150kDa的未知酪氨酸残基磷酸化的蛋白有交叉反应。该单克隆抗体用由合成的人类TrkA蛋白Tyr674位点附近磷酸化肽段免疫动物而制成。Trk受体酪氨酸激酶家族包括TrkA，TrkB和TrkC。这些家庭成员的序列是高度保守的，它们是由不同的神经营养因子激活：NGF激活TrkA，BDNF或NT4激活TrkB，NT3激活TrkC。TrkA调节细胞增殖，神经系统的发育和成熟很重要（1）。在Tyr490磷酸化，需要与Shc结合及Ras-MAP激酶级联的激活。Tyr674/675残基在催化域内，此位点的磷酸化能影响TrkA的激酶活性（2-6）。点突变，缺失和染色体重排（嵌合体）会引起配体依赖受体的二聚化，激活TrkA。许多恶性肿瘤，包括乳腺癌、结肠癌、前列腺癌、甲状腺癌和急性髓细胞白血病有激活的TrkA。神经母细胞瘤的TrkA表达是一个预后良好的指标，因为它标志着肿瘤生长停滞和从神经嵴分化而来（1）。TrkA和TrkB的磷酸化位点保守，人类序列中，TrkA的Tyr490对应TrkB的Tyr512，TrkA的Tyr674/675对应TrkB的Tyr706/707（7）。TrkB在神经母细胞瘤，前列腺癌和胰导管腺癌等肿瘤中过度表达。在神经母细胞瘤中，TrkB的过度表达与疾病的不良预后有关，脑源性神经营养因子（BDNF）的额外过表达通过自分泌循环信号增强了肿瘤的生存。一种选择性剪接截断了TrkB致其缺乏激酶结构域，这种亚型在肾母细胞瘤中过表达，这种亚型可能作为一种TrkB的显性负向信号（8）。

1. Huang, E.J. and Reichardt, L.F. (2003) Annu Rev Biochem 72, 609-42.
2. Segal, R.A. and Greenberg, M.E. (1996) Annu Rev Neurosci 19, 463-89.
3. Stephens, R.M. et al. (1994) Neuron 12, 691-705.
4. Marsh, H.N. et al. (2003) J Cell Biol 163, 999-1010.
5. Obermeier, A. et al. (1993) EMBO J 12, 933-41.
6. Obermeier, A. et al. (1994) EMBO J 13, 1585-90.
7. Arevalo, J.C. et al. (2001) Oncogene 20, 1229-34.
8. Reuther, G.W. et al. (2000) Mol Cell Biol 20, 8655-66.
9. Greco, A. et al. (1997) Genes Chromosomes Cancer 19, 112-23.
10. Pierotti, M.A. and Greco, A. (2006) Cancer Lett 232, 90-8.
11. Lagadec, C. et al. (2009) Oncogene 28, 1960-70.
12. Greco, A. et al. (2010) Mol Cell Endocrinol 321, 44-9.
13. Ødegaard, E. et al. (2007) Hum Pathol 38, 140-6.
14. Huang, E.J. and Reichardt, L.F. (2003) Annu. Rev. Biochem. 72, 609-642.
15. Geiger, T.R. and Peeper, D.S. (2005) Cancer Res 65, 7033-6.
16. Han, L. et al. (2007) Med Hypotheses 68, 407-9.
17. Aoyama, M. et al. (2001) Cancer Lett 164, 51-60.
18. Desmet, C.J. and Peeper, D.S. (2006) Cell Mol Life Sci 63, 755-9.

原厂资料：

Homology

Species predicted to react based on 100% sequence homology: Human, Mouse

Specificity / Sensitivity

Phospho-TrkA (Tyr674/675)/TrkB (Tyr706/707) (C50F3) Rabbit mAb detects endogenous levels of TrkA and TrkB only when phosphorylated at Tyr674/675 of TrkA and Tyr706/707 of TrkB. The antibody may cross-react with a protein of ~150 kDa phosphorylated at an unknown tyrosine residue.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Tyr674/674 of human TrkA.

Background

The family of Trk receptor tyrosine kinases consists of TrkA, TrkB and TrkC. While the sequence of these family members is highly conserved, they 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 (chimeras) cause ligand-independent receptor dimerization and activation of TrkA. Many malignancies including 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 Wilms’s tumors and this isoform may act as a dominant-negative to TrkB signaling (8).

1. Huang, E.J. and Reichardt, L.F. (2003) Annu Rev Biochem 72, 609-42.
2. Segal, R.A. and Greenberg, M.E. (1996) Annu Rev Neurosci 19, 463-89.
3. Stephens, R.M. et al. (1994) Neuron 12, 691-705.
4. Marsh, H.N. et al. (2003) J Cell Biol 163, 999-1010.
5. Obermeier, A. et al. (1993) EMBO J 12, 933-41.
6. Obermeier, A. et al. (1994) EMBO J 13, 1585-90.
7. Arevalo, J.C. et al. (2001) Oncogene 20, 1229-34.
8. Reuther, G.W. et al. (2000) Mol Cell Biol 20, 8655-66.
9. Greco, A. et al. (1997) Genes Chromosomes Cancer 19, 112-23.
10. Pierotti, M.A. and Greco, A. (2006) Cancer Lett 232, 90-8.
11. Lagadec, C. et al. (2009) Oncogene 28, 1960-70.
12. Greco, A. et al. (2010) Mol Cell Endocrinol 321, 44-9.
13. Ødegaard, E. et al. (2007) Hum Pathol 38, 140-6.
14. Huang, E.J. and Reichardt, L.F. (2003) Annu. Rev. Biochem. 72, 609-642.
15. Geiger, T.R. and Peeper, D.S. (2005) Cancer Res 65, 7033-6.
16. Han, L. et al. (2007) Med Hypotheses 68, 407-9.
17. Aoyama, M. et al. (2001) Cancer Lett 164, 51-60.
18. Desmet, C.J. and Peeper, D.S. (2006) Cell Mol Life Sci 63, 755-9.

注意事项：

Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM
NaCl, 100 µg/ml BSA and 50% glycerol. Store at –20°C.
Do not aliquot the antibody