ALK (D5F3?) XP? Rabbit mAb (Biotinylated)

• 产品编号：CST-8936S      品牌：CST       原厂货号：8936S
• 产品分类：抗体 > 一抗 > 表位标签和报告基因特异性抗体
• 应用分类：

描述：

与ALK融合蛋白一样，ALK (D5F3) XP® 兔单抗 (生物素标记)即使在低水平下能够检测内源性水平的总ALK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。该单克隆抗体是通过用重组蛋白免疫动物而制备的，该重组蛋白是人ALK蛋白羧基末端附近的残基。该Cell Signaling Technology公司的抗体在最佳条件下与生物素结合。该抗体与非结合的ALK (D5F3) XP®兔单抗 #3633预期表现出同一物种的交叉反应。间变性淋巴瘤激酶（ALK）是多效生长因子（PTN）的酪氨酸激酶受体，它是大脑胚胎发育过程中的生长因子(1-3)。 在表达ALK的细胞中，PTN诱导ALK及其下游效应因子IRS-1, Shc, PLCγ, 和PI3K激酶发生磷酸化(1)。ALK最初是从易位突变产生的NPM-ALK融合蛋白而被发现的(4)。NPM-ALK融合蛋白是一个组成性活化，有原癌基因活性的间变性淋巴瘤相关酪氨酸激酶(4)。 由NPM-ALK介导的PLCγ的活化可能对有丝分裂活性起到关键作用，并且可能对间变性淋巴瘤的发病过程很重要(5)。另一个完全不同的ALK原癌融合蛋白在非小细胞肺癌细胞株中被报道，该蛋白融合了ALK与EML4（棘皮动物微管结合蛋白样4），其相应融合转录产物在一些肺腺癌中也有表达。在EML4-ALK融合蛋白中，微管相关蛋白EML4的短氨基末端区域和ALK的激酶活性区域融合在一起(6-8)。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 (Biotinylated) 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 protein.

Description

This Cell Signaling Technology antibody is conjugated to biotin under optimal conditions. The biotinylated antibody is expected to exhibit the same species cross-reactivity as the unconjugated ALK (D5F3) XP® Rabbit mAb #3633.

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 136 mM NaCl, 2.6 mM KCI, 12 mM
sodium phosphate (pH 7.4) dibasic, 2 mg/ml BSA, and 50%
glycerol. Store at –20°C. Do not aliquot the antibodies.