Post-translational modifications at the ATP-positioning G-loop that regulate protein kinase activity.
Pharmacol Res
; 135: 181-187, 2018 09.
Article
em En
| MEDLINE
| ID: mdl-30048755
ABSTRACT
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-GlcNAcylation, 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.
Palavras-chave
Texto completo:
1
Coleções:
01-internacional
Base de dados:
MEDLINE
Assunto principal:
Proteínas Quinases
/
Processamento de Proteína Pós-Traducional
Limite:
Animals
/
Humans
Idioma:
En
Revista:
Pharmacol Res
Assunto da revista:
FARMACOLOGIA
Ano de publicação:
2018
Tipo de documento:
Article