Phospho-ALK (Tyr1282/1283) (D39B2) Rabbit mAb

• 产品编号：CST-9687S      品牌：CST       原厂货号：9687S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

只有当Tyr1282/1283(相当于NPM-ALK 的Tyr342/343)磷酸化时，磷酸化ALK (Tyr1282/1283) (D39B2)兔单抗能够检测ALK。该抗体可能与过表达的磷酸化酪氨酸蛋白如EGFR，发生交叉反应。该单克隆抗体是通过用合成磷酸肽免疫动物而制备的，该合成磷酸肽根据人ALK蛋白Tyr1282/1283附近的残基设计。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)。ALK中Tyr1282/1283的磷酸化在Cell Signaling Technology (CST)使用PhosphoScan®,LC-MS/MS平台磷酸化位点发现平台被确定。ALK中Tyr1282/1283的磷酸化在选择性肿瘤细胞系和肿瘤中可发现（6）。

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.

原厂资料：

Homology

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

Specificity / Sensitivity

Phospho-ALK (Tyr1282/1283) (D39B2) Rabbit mAb detects ALK only when phosphorylated at Tyr1282/1283 (equivalent to Tyr342/343 of NPM-ALK). The antibody may cross-react with other overexpressed phospho-tyrosine proteins such as EGFR.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Tyr1282/1283 of human ALK protein.

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).Phosphorylation of ALK at Tyr1282/1283 was identified at Cell Signaling Technology (CST) using PhosphoScan®, CST's LC-MS/MS platform for phosphorylation site discovery. Phosphorylation of ALK at Tyr1282/1283 was observed in select carcinoma cell lines and tumors (6).

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.

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.