Product Pathways - DNA Damage
Phospho-Chk1 (Ser317) Antibody #2344
|W||H R Mk Mi||Endogenous||56||Rabbit|
Reactivity Key: H=Human R=Rat Mk=Monkey Mi=Mink
Species cross-reactivity is determined by western blot. Species enclosed in parentheses are predicted to react based on 100% sequence homology.
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.
Western blot analysis of extracts from HeLa and COS cells treated with HU or UV as indicated, using Phospho-Chk1 (Ser317) Antibody.
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 re-entry 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). Research studies have implicated Chk1 as a drug target for cancer therapy as its inhibition leads to cell death in many cancer cell lines (9).
- Liu, Q. et al. (2000) Genes Dev 14, 1448-59.
- Zhao, H. and Piwnica-Worms, H. (2001) Mol Cell Biol 21, 4129-39.
- Jiang, K. et al. (2003) J Biol Chem 278, 25207-17.
- Martin, S.A. and Ouchi, T. (2008) Mol Cancer Ther 7, 2509-16.
- Chen, M.S. et al. (2003) Mol Cell Biol 23, 7488-97.
- Zeng, Y. et al. (1998) Nature 395, 507-10.
- Löffler, H. et al. (2006) Cell Cycle 5, 2543-7.
- Zachos, G. et al. (2007) Dev Cell 12, 247-60.
- Garber, K. (2005) J Natl Cancer Inst 97, 1026-8.
- Heffernan , T. P. et al. (2002) An ATR- and Chk1-dependent S checkpoint inhibits replicon initiation following UVC-induced DNA damage. Mol. Cell Biol. 22, 8552-8561. Applications: Western Blotting
- Ward, I. M. et al. (2004) UV-induced ataxia-telangiectasia-mutated and Rad3-related (ATR) activation requires replication stress. J. Biol. Chem. 279, 9677-9680. Applications: IC-IF Western Blotting
- Chini, C.C. and Chen, J. (2003) Human claspin is required for replication checkpoint control. J. Biol. Chem. 278, 30057-30062. Applications: IC-ABC Western Blotting
- Buscemi, G. et al. (2006) Mol Cell Biol 26, 7832-45. Applications: Western Blotting
- Batchelor, E. et al. (2011) Mol Syst Biol 7, 488. Applications: Western Blotting
- Nam, E.A. et al. (2011) J Biol Chem 286, 28707-14. Applications: Western Blotting
- Schults, M.A. et al. (2010) J Biol Chem 285, 14558-64. Applications: Western Blotting
- Saldivar, J.C. et al. (2012) PLoS Genet 8, e1003077. Applications: Western Blotting
- Niziolek-Kierecka, M. et al. (2012) Chem Res Toxicol 25, 862-72. Applications: Western Blotting
- Jarvis, I.W. et al. (2013) Toxicol Appl Pharmacol 266, 408-18. Applications: Western Blotting
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For Research Use Only. Not For Use In Diagnostic Procedures.