Journal
PHARMACOLOGICAL RESEARCH
Volume 135, Issue -, Pages 181-187Publisher
ACADEMIC PRESS LTD- ELSEVIER SCIENCE LTD
DOI: 10.1016/j.phrs.2018.07.009
Keywords
Protein kinase; Phosphorylation; ATP-positioning G-loop; Post-translational modifications; Oxidative stress
Categories
Funding
- National Institutes of Health, National Heart, Blood, and Lung Institute [HL112388, HL123061]
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Protein kinases are a superfamily of enzymes that control a wide range of cellular functions. These enzymes share a highly conserved catalytic core that folds into a similar bilobar three-dimensional structure. One highly conserved region in the protein kinase core is the glycine-rich loop (or G-loop), a highly flexible loop that is characterized by a consensus GxGxxG sequence. The G-loop points toward the catalytic cleft and functions to bind and position ATP for phosphotransfer. Of note, in many protein kinases, the second and third glycine residues in the G-loop triad flank residues that can be targets for phosphorylation (Ser, Thr, or Tyr) or other post translational modifications (ubiquitination, acetylation, O-G1cNAcylation, oxidation). There is considerable evidence that cyclin-dependent kinases are held inactive through inhibitory phosphorylation of the conserved Thr/Tyr residues in this position of the G-loop and that dephosphorylation by cellular phosphatases is required for CDK activation and progression through the cell cycle. This review summarizes literature that identifies residues in or adjacent to the G-loop in other protein kinases that are targets for functionally important post translational modifications.
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