Drosophila phosphoinositide-dependent kinase-1 regulates apoptosis and growth via the phosphoinositide 3-kinase-dependent signaling pathway

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dc.contributor.authorCho K.S.ko
dc.contributor.authorLee J.H.ko
dc.contributor.authorKim S.ko
dc.contributor.authorKim D.ko
dc.contributor.authorKoh H.ko
dc.contributor.authorLee J.ko
dc.contributor.authorKim J.ko
dc.contributor.authorChung, Jongkyeongko
dc.contributor.authorKim C.ko
dc.date.accessioned2013-03-03T23:42:52Z-
dc.date.available2013-03-03T23:42:52Z-
dc.date.created2012-02-06-
dc.date.created2012-02-06-
dc.date.issued2001-
dc.identifier.citationPROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA, v.98, no.11, pp.6144 - 6149-
dc.identifier.issn0027-8424-
dc.identifier.urihttp://hdl.handle.net/10203/80952-
dc.description.abstractPhosphoinositide-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 56 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- I, 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.-
dc.languageEnglish-
dc.publisherNATL ACAD SCIENCES-
dc.subject3-PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASE-1-
dc.subjectNF-KAPPA-B-
dc.subjectS6 KINASE-
dc.subjectPHOSPHATIDYLINOSITOL 3-KINASE-
dc.subjectCELL-DEATH-
dc.subjectAKT-
dc.subjectPDK1-
dc.subjectACTIVATION-
dc.subjectPHOSPHORYLATION-
dc.subjectGENE-
dc.titleDrosophila phosphoinositide-dependent kinase-1 regulates apoptosis and growth via the phosphoinositide 3-kinase-dependent signaling pathway-
dc.typeArticle-
dc.identifier.wosid000168883700039-
dc.identifier.scopusid2-s2.0-0007588936-
dc.type.rimsART-
dc.citation.volume98-
dc.citation.issue11-
dc.citation.beginningpage6144-
dc.citation.endingpage6149-
dc.citation.publicationnamePROCEEDINGS OF THE NATIONAL ACADEMY OF SCIENCES OF THE UNITED STATES OF AMERICA-
dc.identifier.doi10.1073/pnas.101596998-
dc.contributor.localauthorKim J.-
dc.contributor.localauthorChung, Jongkyeong-
dc.contributor.nonIdAuthorCho K.S.-
dc.contributor.nonIdAuthorLee J.H.-
dc.contributor.nonIdAuthorKim S.-
dc.contributor.nonIdAuthorKim D.-
dc.contributor.nonIdAuthorKoh H.-
dc.contributor.nonIdAuthorLee J.-
dc.contributor.nonIdAuthorKim C.-
dc.type.journalArticleArticle-
dc.subject.keywordPlus3-PHOSPHOINOSITIDE-DEPENDENT PROTEIN KINASE-1-
dc.subject.keywordPlusNF-KAPPA-B-
dc.subject.keywordPlusS6 KINASE-
dc.subject.keywordPlusPHOSPHATIDYLINOSITOL 3-KINASE-
dc.subject.keywordPlusCELL-DEATH-
dc.subject.keywordPlusAKT-
dc.subject.keywordPlusPDK1-
dc.subject.keywordPlusACTIVATION-
dc.subject.keywordPlusPHOSPHORYLATION-
dc.subject.keywordPlusGENE-
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