Caenorhabditis elegans PIAK, a phospholipid-independent kinase that activates the AKT/PKB survival kinase.
J Biol Chem
; 276(23): 20323-9, 2001 Jun 08.
Article
en En
| MEDLINE
| ID: mdl-11274160
Phospholipid-dependent kinase 1 (PDK 1) is a 3'-phospholipid-responsive serine/threonine kinase that plays a critical role in cell survival by phosphorylating and activating the anti-apoptotic AKT/PKB kinase. While PDK 1 is clearly an important component of the cell survival machinery, the potential for phospholipid-independent activation of the AKT/PKB survival pathway has not been extensively examined at the molecular level. We have identified a second form of PDK 1 in the nematode Caenorhabditis elegans that we have termed PIAK (phospholipid-independent AKT/PKB kinase). PIAK is highly homologous to C. elegans and mammalian PDK 1 with the exception that the novel kinase lacks a phospholipid binding pleckstrin homology domain. The domain structure of PIAK suggests that it might be a phospholipid-independent kinase, and PIAK phosphorylates mammalian AKT/PKB at the activating Thr(308) residue in the presence of the phosphatidylinositol (PI) 3-kinase inhibitors as well as in the absence of growth factors. In addition, PIAK is capable of inducing the phospholipid-independent, AKT/PKB-induced phosphorylation of the AFX-type forkhead transcription factor, resulting in its cytoplasmic localization. Because the nuclear localization of this transcription factor induces an apoptotic state, this PIAK-mediated cytoplasmic sequestration allows for cell survival. Finally, PIAK activity appears to be induced by various inhibitors of cell cycle G(1) progression. These data suggest an alternate, phosphatidylinositol 3-kinase-independent mechanism for the activation of the AKT/PKB survival pathway that may be utilized during periods of cellular quiescence.
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Colección:
01-internacional
Base de datos:
MEDLINE
Asunto principal:
Proteínas Proto-Oncogénicas
/
Proteínas Serina-Treonina Quinasas
/
Caenorhabditis elegans
/
Proteínas de Caenorhabditis elegans
Tipo de estudio:
Prognostic_studies
Límite:
Animals
Idioma:
En
Revista:
J Biol Chem
Año:
2001
Tipo del documento:
Article
Pais de publicación:
Estados Unidos