Cell Signaling Technology

Product Pathways - Tyrosine Kinase / Adaptors

Phospho-HER2/ErbB2 (Tyr1196) (D66B7) Rabbit mAb #6942

erb-b2  

No. Size Price
6942S 100 µl ( 10 western blots ) ¥3,900.00 现货查询 购买询价
6942 carrier free & custom formulation / quantityemail request
Applications Dilution Species-Reactivity Sensitivity MW (kDa) Isotype
W 1:1000 Human,Mouse, Endogenous 185 Rabbit IgG
IP 1:100

Species cross-reactivity is determined by western blot.

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

Specificity / Sensitivity

Phospho-HER2/ErbB2 (Tyr1196) D66B7) Rabbit mAb recognizes endogenous levels of HER2/ErbB2 protein only when phosphorylated at Tyr1196. The antibody may detect other activated ErbB family members.

磷酸化HER2/ErbB2 (Tyr1196) (D66B7) 兔单抗仅在Tyr1196被磷酸化后才能检测到内源性HER2/ErbB2的存在。本抗体可能与其它激活的ErbB家族蛋白发生交叉反应。

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Tyr1196 of human HER2/ErbB2 protein.

单克隆抗体通过用多肽免疫动物得到,该磷酸化多肽是根据人的HER2/ErbB2蛋白Tyr1196附近的氨基酸序列合成的。

Western Blotting

Western Blotting

Western blot analysis of extracts from T47D and MCF7 cells, untreated or treated with human neuregulin-1 #5218 (100 ng/ml, 5 min), using Phospho-HER2/ErbB2 (Tyr1196) (D66B7) Rabbit mAb (upper) and HER2/ErbB2 (29D8) Rabbit mAb #2165 (lower). Western blot法检测下列细胞提取物:未处理的或用human neuregulin-1 #5218 (100 ng/ml, 5 min)处理的T47D 和MCF7细胞。使用抗体为:Phospho-HER2/ErbB2 (Tyr1196) (D66B7) Rabbit mAb (上) 和 HER2/ErbB2 (29D8) Rabbit mAb #2165 (下)。

Background

The ErbB2 (HER2) proto-oncogene encodes a 185 kDa transmembrane, receptor-like glycoprotein with intrinsic tyrosine kinase activity (1). While ErbB2 lacks an identified ligand, ErbB2 kinase activity can be activated in the absence of a ligand when overexpressed and through heteromeric associations with other ErbB family members (2). Amplification of the ErbB2 gene and overexpression of its product are detected in almost 40% of human breast cancers (3). Binding of the c-Cbl ubiquitin ligase to ErbB2 at Tyr1112 leads to ErbB2 poly-ubiquitination and enhances degradation of this kinase (4). ErbB2 is a key therapeutic target in the treatment of breast cancer and other carcinomas and targeting the regulation of ErbB2 degradation by the c-Cbl-regulated proteolytic pathway is one potential therapeutic strategy. Phosphorylation of the kinase domain residue Tyr877 of ErbB2 (homologous to Tyr416 of pp60c-Src) may be involved in regulating ErbB2 biological activity. The major autophosphorylation sites in ErbB2 are Tyr1248 and Tyr1221/1222; phosphorylation of these sites couples ErbB2 to the Ras-Raf-MAP kinase signal transduction pathway (1,5).

原癌基因ErbB2 (HER2)编码185kDa的受体样跨膜糖蛋白,该蛋白具有固有的酪氨酸激酶的活性 (1)。ErbB2的配体目前尚不清楚,但在高表达的ErbB2与其它ErbB家族成员形成异源二聚体时,即使缺少配体,其酶活性仍能被激活(2)。将近40%的人类乳腺癌中能够检测到ErbB2基因的扩增及其产物的过量表达。泛素连接酶c-Cbl结合在ErbB2的Tyr1112上能够导致ErbB2聚泛素化并促进其降解(4)。ErbB2是乳腺癌等多种癌肿的关键治疗靶点,通过c-Cbl介导的蛋白水解途径靶向调控ErbB2的降解是一种潜在的治疗手段。磷酸化ErbB2的激酶位点Tyr877(同源于pp60c-Src 的Tyr416)能调控ErbB2的生物活性。ErbB2的自磷酸化位点是Tyr1248和 Tyr1221/1222,这些位点的磷酸化将ErbB2与Ras-Raf-MAP激酶的信号转导途径联系起来(1,5)。

The autophosphorylation of HER/ErbB2 at Tyr1196 mediates HER2/ErbB2 association with Crk protein and leads to Ras-independent downstream Erk acitvation (6). HER2/ErbB2 phosphorylation at Tyr1196 has been coupled to cell migration and polarity disruption (7,8).

HER/ErbB2在Tyr1196位点的自磷酸化介导HER2/ErbB2与Crk蛋白关联并导致下游Erk以Ras非依赖的途径激活(6)。HER2/ErbB2在Tyr1196位点的磷酸化与细胞的迁移和极性破坏相关(7,8)。

  1. Muthuswamy, S.K. et al. (1999) Mol Cell Biol 19, 6845-57.
  2. Qian, X. et al. (1994) Proc Natl Acad Sci USA 91, 1500-4.
  3. Dittadi, R. and Gion, M. (2000) J Natl Cancer Inst 92, 1443-4.
  4. Klapper, L.N. et al. (2000) Cancer Res 60, 3384-8.
  5. Kwon, Y.K. et al. (1997) J Neurosci 17, 8293-9.
  6. Dankort, D. et al. (2001) Mol Cell Biol 21, 1540-51.
  7. Marone, R. et al. (2004) Nat Cell Biol 6, 515-22.
  8. Lucs, A.V. et al. (2010) Oncogene 29, 174-87.

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Cell Signaling Technology is a trademark of Cell Signaling Technology, Inc.

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