In:
Proceedings of the National Academy of Sciences, Proceedings of the National Academy of Sciences, Vol. 98, No. 11 ( 2001-05-22), p. 6144-6149
Kurzfassung:
Phosphoinositide-dependent kinase-1 (PDK-1) is a central mediator
of the cell signaling between phosphoinositide 3-kinase (PI3K) and various intracellular serine/threonine kinases including
Akt/protein kinase B (PKB), p70 S6 kinases, and protein kinase C. Recent studies with cell transfection experiments have implied that
PDK-1 may be involved in various cell functions including cell growth and apoptosis. However, despite its pivotal role in cellular
signalings, the in vivo functions of PDK-1 in a
multicellular system have rarely been investigated. Here, we have isolated Drosophila PDK-1 ( dPDK-1 )
mutants and characterized the in vivo roles of the
kinase. Drosophila deficient in the dPDK-1 gene exhibited lethality and an apoptotic
phenotype in the embryonic stage. Conversely, overexpression of dPDK-1 increased cell and organ size in a Drosophila PI3K-dependent manner. dPDK-1 not only could activate Drosophila Akt/PKB
( Dakt1 ), but also substitute the in vivo functions of its mammalian ortholog to activate Akt/PKB. This
functional interaction between dPDK-1 and Dakt1 was further confirmed through genetic analyses in Drosophila . On the other hand, cAMP-dependent protein
kinase, which has been proposed as a possible target of dPDK-1 , did not interact with dPDK-1 . In
conclusion, our findings provide direct evidence that dPDK-1 regulates cell growth and apoptosis
during Drosophila development via the PI3K-dependent
signaling pathway and demonstrate our Drosophila system
to be a powerful tool for elucidating the in vivo functions and targets of PDK-1.
Materialart:
Online-Ressource
ISSN:
0027-8424
,
1091-6490
DOI:
10.1073/pnas.101596998
Sprache:
Englisch
Verlag:
Proceedings of the National Academy of Sciences
Publikationsdatum:
2001
ZDB Id:
209104-5
ZDB Id:
1461794-8
SSG:
11
SSG:
12
Permalink
