Phospho-ALK (Tyr1078) (D28B4) Rabbit mAb

• 产品编号：CST-12127S      品牌：CST       原厂货号：12127S
• 产品分类：抗体 > 一抗 > 蛋白特异性一抗
• 应用分类：

描述：

只有当Tyr1078（相当于NPM-ALK中的Tyr138）磷酸化时，磷酸化ALK (Tyr1078) (D28B4) 兔单抗能够识别内源性水平的ALK。该抗体可能与其他过量表达的磷酸化酪氨酸激酶如EGFR和Src，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，该合成磷酸肽是人ALK蛋白Tyr1078附近的残基。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Tyr1078的磷酸化是在Cell Signaling Technology用PhosphoScan®, CST's LC-MS/MS平台确定,该平台用于磷酸化位点的发现。ALK中Tyr1078的磷酸化在选择性癌细胞系和肿瘤中可发现。

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 (Tyr1078) (D28B4) Rabbit mAb recognizes endogenous levels of ALK only when phosphorylated at Tyr1078, which is equivalent to Tyr138 of NPM-ALK. This antibody may cross-react weakly with other overexpressed phospho-tyrosine kinases such as EGFR and Src.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Tyr1078 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).

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.