Phospho-EGF Receptor (Tyr1068) (1H12) Mouse mAb

• 产品编号：CST-2236L      品牌：CST       原厂货号：2236L
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

磷酸化的EGFR (Tyr1068)的小鼠源抗体(1H12)仅在Tyr1068位点被磷酸化后才能检测到内源EGFR的水平。本抗体不识别其它位点磷酸化的EGFR，但可能与激活的ErbB家族的其它蛋白发生交叉反应，并在石蜡包埋组织的平滑肌中有非特异着色。

表皮生长因子（EGF）受体是一个属于HER/ErbB蛋白家族的跨膜酪氨酸激酶。配体的结合导致了受体的二聚化，自磷酸化，下游信号分子的激活，内化以及溶酶体降解 (1,2)。表皮生长因子受体（EGFR）在激酶域Tyr845位点的磷酸化与稳定激活回路有关，并且维持了酶的激活状态，为底物蛋白提供了可结合的表位(3,4)。c-Src与 EGFR 在 Tyr845位点的磷酸化有关(5)。PLCγ的SH2结构域结合到磷酸化的Tyr992位点，将引起PLCγ介导的下游信号通路的激活(6)。EGFR Tyr1045位点的磷酸化则为c-Cbl生成一个主要的停靠位点，这个衔接蛋白将导致受体的泛素化以及EGFR活化后的降解(7,8)。GRB2衔接蛋白则结合到活化后的EGFR磷酸化的Tyr1068位点(9)。一对磷酸化EGFR残基(Tyr1148 and Tyr1173)为Shc支架蛋白提供了停靠点，这两个位点都与MAPK激酶通路的激活有关(2)。EGFR在特定的丝氨酸和苏氨酸残基上的磷酸化减弱了EGFR激酶的活性。EGFR羧基末端残基Ser1046 和 Ser1047被CaM 激酶II磷酸化，这两个丝氨酸任何一个突变都将导致EGFR酪氨酸自身磷酸化的上调(10)。

1. Hackel, P.O. et al. (1999) Curr Opin Cell Biol 11, 184-9.
2. Zwick, E. et al. (1999) Trends Pharmacol Sci 20, 408-12.
3. Cooper, J.A. and Howell, B. (1993) Cell 73, 1051-4.
4. Hubbard, S.R. et al. (1994) Nature 372, 746-54.
5. Biscardi, J.S. et al. (1999) J Biol Chem 274, 8335-43.
6. Emlet, D.R. et al. (1997) J Biol Chem 272, 4079-86.
7. Levkowitz, G. et al. (1999) Mol Cell 4, 1029-40.
8. Ettenberg, S.A. et al. (1999) Oncogene 18, 1855-66.
9. Rojas, M. et al. (1996) J Biol Chem 271, 27456-61.
10. Feinmesser, R.L. et al. (1999) J Biol Chem 274, 16168-73.

原厂资料：

Specificity / Sensitivity

Phospho-EGF Receptor (Tyr1068) (1H12) Mouse mAb detects endogenous levels of EGF receptor only when phosphorylated at Tyr1068. This antibody does not recognize EGF receptor phosphorylated at other sites, but may cross-react with other activated ErbB family members. Non-specific staining of smooth muscle may be observed in paraffin-embedded tissues. 

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Tyr1068 of human EGF receptor. 

Background

The epidermal growth factor (EGF) receptor is a transmembrane tyrosine kinase that belongs to the HER/ErbB protein family. Ligand binding results in receptor dimerization, autophosphorylation, activation of downstream signaling, internalization, and lysosomal degradation (1,2). Phosphorylation of EGF receptor (EGFR) at Tyr845 in the kinase domain is implicated in stabilizing the activation loop, maintaining the active state enzyme, and providing a binding surface for substrate proteins (3,4). c-Src is involved in phosphorylation of EGFR at Tyr845 (5). The SH2 domain of PLCγ binds at phospho-Tyr992, resulting in activation of PLCγ-mediated downstream signaling (6). Phosphorylation of EGFR at Tyr1045 creates a major docking site for c-Cbl, an adaptor protein that leads to receptor ubiquitination and degradation following EGFR activation (7,8). The GRB2 adaptor protein binds activated EGFR at phospho-Tyr1068 (9). A pair of phosphorylated EGFR residues (Tyr1148 and Tyr1173) provides a docking site for the Shc scaffold protein, with both sites involved in MAP kinase signaling activation (2). 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; mutation of either of these serines results in upregulated EGFR tyrosine autophosphorylation (10).

1. Hackel, P.O. et al. (1999) Curr Opin Cell Biol 11, 184-9.
2. Zwick, E. et al. (1999) Trends Pharmacol Sci 20, 408-12.
3. Cooper, J.A. and Howell, B. (1993) Cell 73, 1051-4.
4. Hubbard, S.R. et al. (1994) Nature 372, 746-54.
5. Biscardi, J.S. et al. (1999) J Biol Chem 274, 8335-43.
6. Emlet, D.R. et al. (1997) J Biol Chem 272, 4079-86.
7. Levkowitz, G. et al. (1999) Mol Cell 4, 1029-40.
8. Ettenberg, S.A. et al. (1999) Oncogene 18, 1855-66.
9. Rojas, M. et al. (1996) J Biol Chem 271, 27456-61.
10. Feinmesser, R.L. et al. (1999) J Biol Chem 274, 16168-73.

注意事项：

For Research Use Only. Not For Use In Diagnostic Procedures.

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