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

• DOI: 10.1073/pnas.101596998
• Publication Date: 2002-07-26T14:44:19Z
• Authors: Kyoung Sang Cho; Jun Hee Lee; Sunhong Kim; Dohoon Kim; Hyongjong Koh; Jihyun Lee; Changsoo Kim; Jaeseob Kim; Jongkyeong Chung
• Keywords: ASK1; Phosphoinositide 3-kinase

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, protein C. Recent studies with transfection experiments have implied that PDK-1 may be involved in functions growth apoptosis. However, despite its pivotal role cellular signalings, vivo multicellular system rarely been investigated. Here, we isolated Drosophila ( dPDK-1 ) mutants characterized roles kinase. deficient gene exhibited lethality an apoptotic phenotype embryonic stage. Conversely, overexpression increased organ size PI3K-dependent manner. not only could activate Akt/PKB Dakt1 ), but also substitute mammalian ortholog to Akt/PKB. This functional interaction was further confirmed through genetic analyses . On other hand, cAMP-dependent kinase, which has proposed as possible target , did interact In conclusion, our findings provide direct evidence regulates apoptosis during development via pathway demonstrate powerful tool for elucidating targets PDK-1.