| 货号 | 8117S |
| 供应商 | CST |
| 背景 | The epidermal growth factor (EGF) receptor is a 170 kDa transmembrane tyrosine kinase that belongs to the HER/ErbB protein family. Ligand binding results in receptor dimerization, autophosphorylation, activation of downstream signaling and lysosomal degradation (1,2). EGFR is phosphorylated on multiple tyrosine residues, each of which leads to activation of a specific downstream pathway. Major residues involved in EGFR signaling include: Tyr845, Tyr992, Tyr1045, Tyr1068, Tyr1148 and Tyr1173 (2-9). Phosphorylation of EGFR at specific serine and threonine residues attenuates EGFR kinase activity. EGFR carboxy-terminal residues Ser1046 and Ser1047 are phosphorylated by CaM kinase II; a mutation to either of these serines results in upregulated EGFR tyrosine autophosphorylation (10). The ErbB2 (HER2) proto-oncogene encodes a 185 kDa transmembrane, receptor-like glycoprotein with intrinsic tyrosine kinase activity (11). 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 (12). Amplification of the ErbB2 gene and overexpression of its product are detected in almost 40% of human breast cancers, making it a key therapeutic target (13). ErbB2 has several key residues that are phosphorylated upon its activation including Tyr877, Tyr1221/1222 and Tyr1248 (11,14). HER3/ErbB3 is a member of the ErbB receptor protein tyrosine kinase family that lacks tyrosine kinase activity. Tyrosine phosphorylation of ErbB3 depends on its association with other ErbB tyrosine kinases. Ligand binding promotes formation of a heterodimer containing ErbB3 and another ErbB protein and subsequent tyrosine phosphorylation of ErbB3 by the activated ErbB kinase (15,16). At least nine putative carboxy-terminal tail tyrosine phosphorylation sites are found in ErbB3, including Tyr1222 and Tyr1289 (17). ErbB3 may function as an oncogenic unit together with other ErbB members in tumor development; ErbB2 requires ErbB3 to drive breast tumor cell proliferation (18). A novel anti-tumor strategy involves inhibiting the interaction between ErbB3 and ErbB tyrosine kinases. |
| 存放说明 | 4C |
| 参考文献 | 1 . Hackel, P.O. et al. (1999) Curr Opin Cell Biol 11, 184-9. 2 . Muthuswamy, S.K. et al. (1999) Mol Cell Biol 19, 6845-57. 3 . Yarden, Y. and Sliwkowski, M.X. (2001) Nat Rev Mol Cell Biol 2, 127-37. 4 . Zwick, E. et al. (1999) Trends Pharmacol Sci 20, 408-12. 5 . Qian, X. et al. (1994) Proc Natl Acad Sci USA 91, 1500-4. 6 . Guy, P.M. et al. (1994) Proc Natl Acad Sci U S A 91, 8132-6. 7 . Cooper, J.A. and Howell, B. (1993) Cell 73, 1051-4. 8 . Dittadi, R. and Gion, M. (2000) J Natl Cancer Inst 92, 1443-4. 9 . Hubbard, S.R. et al. (1994) Nature 372, 746-54. 10 . Kim, H.H. et al. (1994) J Biol Chem 269, 24747-55. 11 . Biscardi, J.S. et al. (1999) J Biol Chem 274, 8335-43. 12 . Kwon, Y.K. et al. (1997) J Neurosci 17, 8293-9. 13 . Emlet, D.R. et al. (1997) J Biol Chem 272, 4079-86. 14 . Levkowitz, G. et al. (1999) Mol Cell 4, 1029-40. 15 . Holbro, T. et al. (2003) Proc Natl Acad Sci U S A 100, 8933-8. 16 . Ettenberg, S.A. et al. (1999) Oncogene 18, 1855-66. 17 . Rojas, M. et al. (1996) J Biol Chem 271, 27456-61. 18 . Feinmesser, R.L. et al. (1999) J Biol Chem 274, 16168-73. |
Immunohistochemical analysis of paraffin-embedded SK-BR-3 cell pellets, either untreated (upper) or hEGF-treated #8916 (lower), using Phospho-EGF Receptor (Tyr1068) (D7A5) XP® Rabbit mAb #3777, Phospho-HER2/ErbB2 (Tyr1221/1222) (6B12) Rabbit mAb #2243, Phopho-HER3/ErbB3 (Tyr1289) (D1B5) Rabbit mAb #2842 or EGF Receptor (D38B1) XP® Rabbit mAb #4267. Cell pellets are provided in the SignalSlide® ErbB Family IHC Controls.免疫组织化学方法检测石蜡包埋的SK-BR-3细胞球，细胞不处理（上图）或hEGF-treated #8916处理(下图)，使用的抗体为Phospho-EGF Receptor (Tyr1068) (D7A5) XP® Rabbit mAb #3777, Phospho-HER2/ErbB2 (Tyr1221/1222) (6B12) Rabbit mAb #2243, Phopho-HER3/ErbB3 (Tyr1289) (D1B5) Rabbit mAb #2842 或EGF Receptor (D38B1) XP® Rabbit mAb #4267.细胞球由SignalSlide® ErbB家族IHC对照提供。 | |
