Phosphoinositide-dependent kinase-1 orthologues from five eukaryotes are activated by the hydrophobic motif in AGC kinases.
Biochem Biophys Res Commun
; 321(4): 823-7, 2004 Sep 03.
Article
en En
| MEDLINE
| ID: mdl-15358101
ABSTRACT
Phosphoinositide-dependent kinase-1 (PDK1) mediates activation of many AGC kinases by docking onto a phosphorylated hydrophobic motif located C-terminal of the catalytic domain in the AGC kinase. The interaction shifts PDK1 into a conformation with increased catalytic activity and leads to autophosphorylation of PDK1. We demonstrate here that addition of a hydrophobic motif peptide increases the catalytic activity of PDK1 orthologues from Homo sapiens, Aplysia californica, Arabidopsis thaliana, Schizosaccharomyces pombe (ksg1), and Saccharomyces cerevisiae (Pkh1 and Pkh2) 2- to 12-fold. Furthermore, the hydrophobic motif peptide increases autophosphorylation of PDK1 from Homo sapiens, S. pombe, and S. cerevisiae (Phk2). Our results suggest that PDK1 interaction and activation by the hydrophobic motif of AGC kinases is a central mechanism in PDK1 function, which is conserved during eukaryotic evolution.
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Colección:
01-internacional
Banco de datos:
MEDLINE
Asunto principal:
Proteínas Quinasas
/
Proteínas Serina-Treonina Quinasas
Límite:
Animals
/
Humans
Idioma:
En
Revista:
Biochem Biophys Res Commun
Año:
2004
Tipo del documento:
Article
País de afiliación:
Dinamarca