Phospho-Chk1 (Ser317) Antibody

• 产品编号：CST-2344S      品牌：CST       原厂货号：2344S
• 产品分类：抗体 > 一抗 > 磷酸化抗体
• 应用分类：

描述：

Phospho-Chk1 (Ser317) Antibody 能够检测内源性丝氨酸（317位）磷酸化的Chk1蛋白。该抗体不与其他位点磷酸化的Chk1蛋白发生交叉反应。该多克隆抗体是由合成的人源的针对Chk1蛋白丝氨酸（317位）的磷酸化肽段免疫动物，采用蛋白A和多肽亲和层析技术纯化生产的。

Chk1激酶能够充当ATM/ATR激酶的下游并在DNA损伤检验点控制、胚胎发育和肿瘤抑制中发挥重要作用(1)。Chk1的激活涉及317位和345位丝氨酸的磷酸化，其发生响应DNA复制阻滞和某些类型的基因毒性应激反应(2)。尽管345位丝氨酸的磷酸化有助于伴随检验点激活的Chk1定位到核，317位丝氨酸的磷酸化连同位点特异性的PTEN磷酸化允许DNA复制停滞引起的细胞周期折返(4)。Chk1发挥其细胞周期检验点调节机制部分经由调控磷酸酶家族的cdc25。Chk1磷酸化cdc25A后靶向蛋白降解并通过14-3-3的结合抑制自身的活性(5)。激活的chk1能够通过216位丝氨酸的磷酸化失活cdc25C，阻塞cdc2的激活和有丝分裂转换的进入(6)。中心体的chk1被认为可以磷酸化cdc25B并抑制其激活CDK1-cyclin B1，藉此废除有丝分裂纺锤体的形成和染色质凝聚(7)。此外，Chk1通过调节Aurora B和BubR1在纺锤体检验点功能中发挥重要作用(8)。鉴于Chk1的抑制作用能够引起许多肿瘤细胞系的死亡，它已经成为肿瘤治疗中心的药物靶点(9)。

1. Liu, Q. et al. (2000) Genes Dev 14, 1448-59.
2. Zhao, H. and Piwnica-Worms, H. (2001) Mol Cell Biol 21, 4129-39.
3. Jiang, K. et al. (2003) J Biol Chem 278, 25207-17.
4. Martin, S.A. and Ouchi, T. (2008) Mol Cancer Ther 7, 2509-16.
5. Chen, M.S. et al. (2003) Mol Cell Biol 23, 7488-97.
6. Zeng, Y. et al. (1998) Nature 395, 507-10.
7. Löffler, H. et al. (2006) Cell Cycle 5, 2543-7.
8. Zachos, G. et al. (2007) Dev Cell 12, 247-60.
9. Garber, K. (2005) J Natl Cancer Inst 97, 1026-8.

原厂资料：

Specificity / Sensitivity

Phospho-Chk1 (Ser317) Antibody detects endogenous levels of Chk1 only when phosphorylated at Ser317. The antibody does not recognize Chk1 phosphorylated at other sites.

Source / Purification

Polyclonal antibodies are produced by immunizing animals with a synthetic phosphopeptide corresponding to residues surrounding Ser317 of human Chk1. Antibodies are purified by protein A and peptide affinity chromatography. 

Background

Chk1 kinase acts downstream of ATM/ATR kinase and plays an important role in DNA damage checkpoint control, embryonic development, and tumor suppression (1). Activation of Chk1 involves phosphorylation at Ser317 and Ser345 and occurs in response to blocked DNA replication and certain forms of genotoxic stress (2). While phosphorylation at Ser345 serves to localize Chk1 to the nucleus following checkpoint activation (3), phosphorylation at Ser317 along with site-specific phosphorylation of PTEN allows for reentry into the cell cycle following stalled DNA replication (4). Chk1 exerts its checkpoint mechanism on the cell cycle, in part, by regulating the cdc25 family of phosphatases. Chk1 phosphorylation of cdc25A targets it for proteolysis and inhibits its activity through 14-3-3 binding (5). Activated Chk1 can inactivate cdc25C via phosphorylation at Ser216, blocking the activation of cdc2 and transition into mitosis (6). Centrosomal Chk1 has been shown to phosphorylate cdc25B and inhibit its activation of CDK1-cyclin B1, thereby abrogating mitotic spindle formation and chromatin condensation (7). Furthermore, Chk1 plays a role in spindle checkpoint function through regulation of Aurora B and BubR1 (8). Chk1 has emerged as a drug target for cancer therapy as its inhibition leads to cell death in many cancer cell lines (9).

1. Liu, Q. et al. (2000) Genes Dev 14, 1448-59.
2. Zhao, H. and Piwnica-Worms, H. (2001) Mol Cell Biol 21, 4129-39.
3. Jiang, K. et al. (2003) J Biol Chem 278, 25207-17.
4. Martin, S.A. and Ouchi, T. (2008) Mol Cancer Ther 7, 2509-16.
5. Chen, M.S. et al. (2003) Mol Cell Biol 23, 7488-97.
6. Zeng, Y. et al. (1998) Nature 395, 507-10.
7. Löffler, H. et al. (2006) Cell Cycle 5, 2543-7.
8. Zachos, G. et al. (2007) Dev Cell 12, 247-60.
9. Garber, K. (2005) J Natl Cancer Inst 97, 1026-8.

注意事项：

Storage: Supplied in 10 mM sodium HEPES (pH 7.5), 150 mM
NaCl, 100 µg/ml BSA and 50% glycerol. Store at –20°C.
Do not aliquot the antibody.