ALK (D5F3?) XP? Rabbit mAb

• 产品编号：CST-3633P      品牌：Cell Signaling Technology       原厂货号：3633P
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

ALK (D5F3) XP®兔单抗即使在低表达水平下能够检测内源性水平的总ALK蛋白以及ALK融合蛋白，如EML4-ALK变体和NPM-ALK。该抗体不与其他家族成员发生交叉反应。该单克隆抗体通过用重组蛋白免疫动物制备，该重组蛋白是人ALK羧基末端的残基。Met作为肝细胞生长因子 (HGF, 亦作扩散因子) 的高亲和性酪氨酸激酶受体是一个二硫键连接的异二聚体，含有一个45 kDa的 α-亚基和一个145 kDa的 β-亚基 (1,2)。α-亚基和β-亚基的氨基端形成胞外区，β-亚基的其余部分跨细胞膜并且含有一个具有激酶活性的胞内区。Met和HGF相互作用会导致多个酪氨酸位点的自磷酸化，继而招募下游信号分子Gab1, c-Cbl和 PI3 K激酶（3）。这一系列基础性事件对于Met激酶相关的所有生物学功能十分重要。胞内Tyr1003位点的磷酸化对于Met的泛素化和降解是必须的（4）。激酶结构域Tyr1234/1235的磷酸化对于Met的激酶活性十分关键。胞内 Tyr1349的磷酸化为Met提供了Gab1 的直接结合位点(5)。在肾、结肠和乳腺癌中发现有Met水平和/或激酶活性的改变，因此Met是肿瘤治疗和诊断的一个靶点（6,7）。研究发现ALK与其他融合伴侣的易位，如TRK-融合基因（TFG）和KIF5B，也与非小细胞肺癌有关（6,7）。特别是EML4-ALK融合蛋白已经在3-7％的非小细胞肺癌样品中被发现（6-14）。

1. Stoica, G.E. et al. (2001) J Biol Chem 276, 16772-9.
2. Iwahara, T. et al. (1997) Oncogene 14, 439-49.
3. Morris, S.W. et al. (1997) Oncogene 14, 2175-88.
4. Morris, S.W. et al. (1994) Science 263, 1281-4.
5. Bai, R.Y. et al. (1998) Mol Cell Biol 18, 6951-61.
6. Rikova, K. et al. (2007) Cell 131, 1190-203.
7. Takeuchi, K. et al. (2008) Clin Cancer Res 14, 6618-24.
8. Soda, M. et al. (2007) Nature 448, 561-6.
9. Takeuchi, K. et al. (2009) Clin Cancer Res 15, 3143-9.
10. Palmer, R.H. et al. (2009) Biochem J 420, 345-61.
11. Horn, L. and Pao, W. (2009) J Clin Oncol 27, 4232-5.
12. Rodig, S.J. et al. (2009) Clin Cancer Res 15, 5216-23.
13. Mino-Kenudson, M. et al. (2010) Clin Cancer Res 16, 1561-71.
14. Kwak, E.L. et al. (2010) N Engl J Med 363, 1693-703.

原厂资料：

Specificity / Sensitivity

ALK (D5F3) XP® Rabbit mAb detects endogenous levels of total ALK protein as well as ALK fusion proteins, such as EML4-ALK variants and NPM-ALK, even at low levels. This antibody does not cross-react with other family members.

Source / Purification

Monoclonal antibody is produced by immunizing animals with recombinant protein corresponding to residues in the carboxy terminus of human ALK.

Background

Anaplastic lymphoma kinase (ALK) is a tyrosine kinase receptor for pleiotrophin (PTN), a growth factor involved in embryonic brain development (1-3). In ALK-expressing cells, PTN induces phosphorylation of both ALK and the downstream effectors IRS-1, Shc, PLCγ, and PI3 kinase (1). ALK was originally discovered as a nucleophosmin (NPM)-ALK fusion protein produced by a translocation (4). Investigators have found that the NPM-ALK fusion protein is a constitutively active, oncogenic tyrosine kinase associated with anaplastic lymphoma (4). Research literature suggests that activation of PLCγ by NPM-ALK may be a crucial step for its mitogenic activity and involved in the pathogenesis of anaplastic lymphomas (5). 
 A distinct ALK oncogenic fusion protein involving ALK and echinoderm microtubule-associated protein like 4 (EML4) has been described in the research literature from a non-small cell lung cancer (NSCLC) cell line, with corresponding fusion transcripts present in some cases of lung adenocarcinoma. The short, amino-terminal region of the microtubule-associated protein EML4 is fused to the kinase domain of ALK (6-8).

Investigators have identified ALK translocations with other fusion partners, such as TRK-fused gene (TFG) and KIF5B, which have also been associated with NSCLC (6,7). In particular, the EML4-ALK fusion protein has been found in 3-7% of NSCLC samples (6-14).

1. Stoica, G.E. et al. (2001) J Biol Chem 276, 16772-9.
2. Iwahara, T. et al. (1997) Oncogene 14, 439-49.
3. Morris, S.W. et al. (1997) Oncogene 14, 2175-88.
4. Morris, S.W. et al. (1994) Science 263, 1281-4.
5. Bai, R.Y. et al. (1998) Mol Cell Biol 18, 6951-61.
6. Rikova, K. et al. (2007) Cell 131, 1190-203.
7. Takeuchi, K. et al. (2008) Clin Cancer Res 14, 6618-24.
8. Soda, M. et al. (2007) Nature 448, 561-6.
9. Takeuchi, K. et al. (2009) Clin Cancer Res 15, 3143-9.
10. Palmer, R.H. et al. (2009) Biochem J 420, 345-61.
11. Horn, L. and Pao, W. (2009) J Clin Oncol 27, 4232-5.
12. Rodig, S.J. et al. (2009) Clin Cancer Res 15, 5216-23.
13. Mino-Kenudson, M. et al. (2010) Clin Cancer Res 16, 1561-71.
14. Kwak, E.L. et al. (2010) N Engl J Med 363, 1693-703.

注意事项：

Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM NaCl, 100 µg/ml BSA, 50% glycerol and less than 0.02% sodium azide. Store at –20°C. Do not aliquot the antibody.