Phospho-EphA3 (Tyr779) (D10H1) Rabbit mAb

• 产品编号：CST-8862S      品牌：CST       原厂货号：8862S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

只有当Tyr779磷酸化时，磷酸化EphA3 (Tyr779) (D10H1) 兔单抗能够识别内源性水平的EphA3蛋白。该抗体与EphA2, EphA4和EphA5在相应的磷酸位点发生交叉反应。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EphA3蛋白Tyr779附近的残基。Eph受体是研究的最为清楚的酪氨酸激酶受体家族(RTKs)。根据其序列的相似性和一子集配体的倾向性可将它们分为两组：结合基磷脂酰肌醇锚定的麻黄素A配体的EphA受体； 结合具有跨膜区和胞内区的麻黄素B蛋白的EphB 受体(1,2)。Eph 受体及其配体与多种疾病相关，包括肿瘤（3）。Eph A 和B配体都有双重功能。作为RTK配体，麻黄素激活Eph受体的激酶活性以及激活表达该受体细胞的信号通路。麻黄素的胞外区的聚集足以完成这项功能（4）。麻黄素的第二项功能称为“反向信号调节”，凭借胞内区的酪氨酸磷酸化，能够与表达配体的细胞中许多激活信号通路的其它蛋白相互作用（5）。EPHA3受体优先与ephrin-A5结合。该配体-受体的相互作用刺激EphA3信号传导，调节细胞黏附和迁移，诱导细胞形态学反应（6-8）。EphA3在胼胝体轴突导向（9），视网膜和神经元的映射（10）以及心脏细胞迁移和分化中起着至关重要的作用（11）。调查显示，在EphA3功能结构域的体细胞突变与肺癌演变有关（12）。此外，EphA3的表达水平与肿瘤血管生成，胃癌和大肠癌演变有关联（13,14）。Tyr602和Tyr779的磷酸化都涉及ephrin-A5诱导的EphA3的受体活化（15）。EphA3受体中Tyr779的磷酸化是SH2结构域包含Crk适配器的结合位点，这反过来又激活小GTP酶RhoA蛋白（16）。

1. Wilkinson, D.G. (2000) Int Rev Cytol 196, 177-244.
2. Klein, R. (2001) Curr Opin Cell Biol 13, 196-203.
3. Dodelet, V.C. and Pasquale, E.B. (2000) Oncogene 19, 5614-9.
4. Holder, N. and Klein, R. (1999) Development 126, 2033-44.
5. Brückner, K. et al. (1997) Science 275, 1640-3.
6. Smith, L.M. et al. (2004) Exp Cell Res 292, 295-303.
7. Clifford, N. et al. (2008) J Cell Biochem 105, 1250-9.
8. Vearing, C. et al. (2005) Cancer Res 65, 6745-54.
9. Nishikimi, M. et al. (2011) J Neurosci 31, 16251-60.
10. Connor, R.J. et al. (1998) Dev Biol 193, 21-35.
11. Li, Y.Y. et al. (1998) Am J Physiol 274, H331-41.
12. Lisabeth, E.M. et al. (2012) Biochemistry 51, 1464-75.
13. Xi, H.Q. et al. (2012) J Gastroenterol 47, 785-94.
14. Xi, H.Q. and Zhao, P. (2011) J Clin Pathol 64, 498-503.
15. Shi, G. et al. (2010) Cell Res 20, 1263-75.
16. Lawrenson, I.D. et al. (2002) J Cell Sci 115, 1059-72.

原厂资料：

Homology

Species predicted to react based on 100% sequence homology: Mouse, Rat

Specificity / Sensitivity

Phospho-EphA3 (Tyr779) (D10H1) Rabbit mAb recognizes endogenous levels of EphA3 protein only when phosphorylated at Tyr779. This antibody cross-reacts with EphA2, EphA4, and EphA5 at the corresponding phosphosites.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Tyr779 of human EphA3 protein.

Background

The Eph receptors are the largest known family of receptor tyrosine kinases (RTKs). They can be divided into two groups based on sequence similarity and on their preference for a subset of ligands. While EphA receptors bind to a glycosylphosphatidylinositol-anchored ephrin A ligand, EphB receptors bind to ephrin B proteins that have a transmembrane and cytoplasmic domain (1,2). Research studies have shown that Eph receptors and ligands may be involved in many diseases including cancer (3). Both ephrin A and B ligands have dual functions. As RTK ligands, ephrins stimulate the kinase activity of Eph receptors and activate signaling pathways in receptor-expressing cells. The ephrin extracellular domain is sufficient for this function as long as it is clustered (4). The second function of ephrins has been described as "reverse signaling", whereby the cytoplasmic domain becomes tyrosine phosphorylated, allowing interactions with other proteins that may activate signaling pathways in the ligand-expressing cells (5). 
 The EphA3 receptor preferentially binds ephrin-A5. This ligand-receptor interaction stimulates EphA3 signaling, regulates cell adhesion and migration, and induces cellular morphologic responses (6-8). EphA3 plays a critical role in callosal axon guidance (9), retinotectal mapping of neurons (10), as well as cardiac cell migration and differentiation (11). Investigators have shown that somatic mutations in functional domains of EphA3 are linked to lung cancer progression (12). In addition, EphA3 expression levels have been correlated with tumor angiogenesis and progression in gastric and colorectal carcinoma (13,14).Both Tyr602 and Tyr779 phosphorylation are involved in ephrin-A5 induced EphA3 receptor activation (15). Phosphorylated Tyr779 of the EphA3 receptor is the binding site for the SH2-domain-containing Crk adaptor, which in turn activates the small GTPase RhoA (16).

1. Wilkinson, D.G. (2000) Int Rev Cytol 196, 177-244.
2. Klein, R. (2001) Curr Opin Cell Biol 13, 196-203.
3. Dodelet, V.C. and Pasquale, E.B. (2000) Oncogene 19, 5614-9.
4. Holder, N. and Klein, R. (1999) Development 126, 2033-44.
5. Brückner, K. et al. (1997) Science 275, 1640-3.
6. Smith, L.M. et al. (2004) Exp Cell Res 292, 295-303.
7. Clifford, N. et al. (2008) J Cell Biochem 105, 1250-9.
8. Vearing, C. et al. (2005) Cancer Res 65, 6745-54.
9. Nishikimi, M. et al. (2011) J Neurosci 31, 16251-60.
10. Connor, R.J. et al. (1998) Dev Biol 193, 21-35.
11. Li, Y.Y. et al. (1998) Am J Physiol 274, H331-41.
12. Lisabeth, E.M. et al. (2012) Biochemistry 51, 1464-75.
13. Xi, H.Q. et al. (2012) J Gastroenterol 47, 785-94.
14. Xi, H.Q. and Zhao, P. (2011) J Clin Pathol 64, 498-503.
15. Shi, G. et al. (2010) Cell Res 20, 1263-75.
16. Lawrenson, I.D. et al. (2002) J Cell Sci 115, 1059-72.

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.