Phospho-EphA2 (Ser897) (D9A1) Rabbit mAb

• 产品编号：CST-6347S      品牌：CST       原厂货号：6347S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

只有当丝氨酸（897位）磷酸化时，磷酸化EphA2 (Ser897) (D9A1) 兔单抗能够识别内源性水平的EphA2蛋白。该单克隆抗体通过用合成磷酸肽免疫动物制备，该合成磷酸肽是人EphA2蛋白丝氨酸（897位）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）。许多刺激都能使麻黄素B的酪氨酸位点磷酸化，包括与麻黄素B受体结合、Src激酶的激活以及受PDGF和 FGF刺激 (6)。酪氨酸 324/327的磷酸化被认为是体内麻黄素 B1的主要磷酸化位点（7）。已经证明，EphA2的过表达导致的配体依赖促进细胞迁移需要由Akt磷酸化EphA2磷酸化丝氨酸（897位）。另一方面，用其配体Ephrin-A1刺激EphA2，通过生长因子取消Akt的活化，导致EphA2在丝氨酸（897位）去磷酸化（8）。

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. Palmer, A. et al. (2002) Mol Cell 9, 725-37.
7. Kalo, M.S. et al. (2001) J Biol Chem 276, 38940-8.
8. Miao, H. et al. (2009) Cancer Cell 16, 9-20.

原厂资料：

Homology

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

Specificity / Sensitivity

Phospho-EphA2 (Ser897) (D9A1) Rabbit mAb recognizes endogenous levels of EphA2 protein only when phosphorylated at Ser897.

Source / Purification

Monoclonal antibody is produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Ser897 of human EphA2 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: 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). Various stimuli can induce tyrosine phosphorylation of ephrin B, including binding to EphB receptors, activation of Src kinase, and stimulation by PDGF and FGF (6). Tyr324 and Tyr327 have been identified as major phosphorylation sites of ephrin B1 in vivo (7).It has been demonstrated that ligand-independent promotion of cell migration by EphA2 overexpression requires phosphorylation of EphA2 at Ser897 by Akt. On the other hand, stimulation of EphA2 by its ligand Ephrin-A1 negates Akt activation by growth factors and causes EphA2 dephosphorylation at Ser897 (8).

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. Palmer, A. et al. (2002) Mol Cell 9, 725-37.
7. Kalo, M.S. et al. (2001) J Biol Chem 276, 38940-8.
8. Miao, H. et al. (2009) Cancer Cell 16, 9-20.

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.