Phospho-ALK (Tyr1278/1282/1283) Antibody

• 产品编号：CST-3983S      品牌：CST       原厂货号：3983S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

磷酸化ALK(Tyr1278/1282/1283)抗体仅在Tyr1278/1282/1283（对应NPM-ALK上Tyr338/342/343）被磷酸化后才能检测到ALK的存在。本抗体在ALK的Tyr1283单独被磷酸化时有轻微的交叉反应，也能与Tyr672/676/677位点磷酸化的白细胞酪氨酸激酶（LTK）反应。多克隆抗体通过合成磷酸化多肽免疫动物得到，该多肽是根据人的ALK蛋白Tyr1278/1282/1283 附近的氨基酸序列合成的。抗体经过protein A和肽亲和层析。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，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(6,7)。ALK的Tyr1278/Tyr1282/Tyr1283 位点磷酸化是Cell Signaling Technology (CST)公司利用LC-MS/MS平台PhosphoScan®技术在寻找磷酸化位点过程中发现的。ALK的Tyr1278/Tyr1282/Tyr1283 位点磷酸化在某些肿瘤及肿瘤细胞系中存在(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

Specificity / Sensitivity

Phospho-ALK (Tyr1278/1282/1283) Antibody detects ALK only when phosphorylated at Tyr1278/1282/1283, which is equivalent to Tyr338/342/343 of NPM-ALK. This antibody might also have slight reactivity toward ALK when it is phosphorylated at Tyr1283 alone. This antibody also reacts with leukocyte tyrosine kinase (LTK) phosphorylated at Tyr672/676/677.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Tyr1278/1282/1283 of human ALK protein. Antibodies are purified by protein A and peptide affinity chromatography.

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 an NPM (nucleophosmin)-ALK fusion protein produced by a translocation (4). The NPM-ALK fusion protein is a constitutively active, oncogenic tyrosine kinase associated with anaplastic lymphoma (4). Activation of PLCγ by NPM-ALK has been suggested to be a crucial step for its mitogenic activity and may be important in the pathogenesis of anaplastic lymphomas (5). A distinct ALK oncogenic fusion protein involving ALK and EML4 has been described from a non-small cell lung cancer 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 (6,7).Phosphorylation of ALK on Tyr1278/Tyr1282/Tyr1283 was identified at Cell Signaling Technology (CST) using PhosphoScan®, CST's LC-MS/MS platform for phosphorylation site discovery. Phosphorylation of ALK at these three sites was observed in select carcinoma cell lines and in 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 and 50% glycerol. Store at –20°C.
Do not aliquot the antibody.