Cell Signaling Technology

Product Pathways - Tyrosine Kinase / Adaptors

Phospho-ALK (Tyr1604) Antibody #3341

NPM-ALK  

No. Size Price
3341L 300 µl ( 30 western blots ) ¥8,792.00 现货查询 购买询价
3341S 100 µl ( 10 western blots ) ¥3,900.00 现货查询 购买询价
3341 carrier free & custom formulation / quantityemail request
Applications Dilution Species-Reactivity Sensitivity MW (kDa) Isotype
W 1:1000 Human, Endogenous 80 (NPM-ALK) 220 (ALK) Rabbit
IP 1:50

Species cross-reactivity is determined by western blot.

Applications Key: W=Western Blotting, IP=Immunoprecipitation,

Specificity / Sensitivity

Phospho-ALK (Tyr1604) Antibody detects ALK only when phosphorylated at Tyr1604 (equivalent to Tyr664 of NPM-ALK). This antibody may cross-react with other activated protein tyrosine kinases including EGFR. 磷酸化的ALK(Tyr1604)抗体仅在Tyr1604(对应NPM-ALK上Tyr664)被磷酸化后才能检测到ALK的存在。本抗体与其它激活的酪氨酸激酶(包括EGFR)有交叉反应。

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Tyr1604 of human ALK. Antibodies are purified by protein A and peptide affinity chromatography 多克隆抗体通过用合成磷酸化多肽免疫动物得到,该多肽是根据人的ALK蛋白Tyr1604附近的氨基酸序列合成的。抗体经过protein A和亲和色谱纯化。

Western Blotting

Western Blotting

Western blot analysis of extracts from Sup-M2 cells, using Phospho-ALK (Tyr1604) Antibody (A,B) or ALK Antibody (C,D). The phospho-specificity of the antibody was characterized by treating the membrane with calf intestinal alkaline phosphatase (CIP) (B,D) after Western transfer. (Sup-M2 cells provided by Dr. Stephan W. Morris, St. Jude Children's Research Hospital, Tennessee.) 用抗磷酸化的ALK (Tyr1604)的抗体(A, B)或抗ALK的抗体(C, D)对Sup-M2细胞提取物进行蛋白质印记检测。转膜后用小牛肠碱性磷酸酶(CIP)对膜进行处理(B, D),可以检测磷酸化抗体的特异性。(Sup-M2 细胞由St. Jude Children's Research Hospital, Tennessee 的 Stephan W. Morris 博士提供。)

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).

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)。

Phosphorylated Tyr664 of NPM-ALK (equivalent to Tyr1604 of full length ALK) is required for the interaction with PLCgamma (5). Site-directed mutagenesis of this tyrosine residue results in the loss of oncogenic activity of NPM-ALK (5).

NPM-ALK蛋白上Tyr664(对应全长ALK上Tyr1604)的磷酸化对于其和PLCgamma相互作用是必须的(5)。该酪氨酸位点的定点突变会导致NPM-ALK失去原癌基因活性(5)。

  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.

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