David Cortez
Faculty Member
Last active: 2/4/2016

Thr-1989 phosphorylation is a marker of active ataxia telangiectasia-mutated and Rad3-related (ATR) kinase.

Nam EA, Zhao R, Glick GG, Bansbach CE, Friedman DB, Cortez D
J Biol Chem. 2011 286 (33): 28707-14

PMID: 21705319 · PMCID: PMC3190678 · DOI:10.1074/jbc.M111.248914

The DNA damage response kinases ataxia telangiectasia-mutated (ATM), DNA-dependent protein kinase (DNA-PK), and ataxia telangiectasia-mutated and Rad3-related (ATR) signal through multiple pathways to promote genome maintenance. These related kinases share similar methods of regulation, including recruitment to specific nucleic acid structures and association with protein activators. ATM and DNA-PK also are regulated via phosphorylation, which provides a convenient biomarker for their activity. Whether phosphorylation regulates ATR is unknown. Here we identify ATR Thr-1989 as a DNA damage-regulated phosphorylation site. Selective inhibition of ATR prevents Thr-1989 phosphorylation, and phosphorylation requires ATR activation. Cells engineered to express only a non-phosphorylatable T1989A mutant exhibit a modest ATR functional defect. Our results suggest that, like ATM and DNA-PK, phosphorylation regulates ATR, and phospho-peptide specific antibodies to Thr-1989 provide a proximal marker of ATR activation.

MeSH Terms (11)

Animals Ataxia Telangiectasia Mutated Proteins Cell Cycle Proteins DNA-Binding Proteins DNA Damage Enzyme Activation Humans Phosphorylation Protein-Serine-Threonine Kinases Threonine Tumor Suppressor Proteins

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