Regulation of Drosophila tracheal system development by protein kinase B.
Protein kinase B (PKB, also termed Akt) is a phosphatidylinositol 3' kinase (PI3'K)-dependent enzyme implicated in survival signaling and human tumorigenesis. To identify potential targets of this protein kinase, we employed a genetic screen in Drosophila. Among several genes that genetically interacted with PKB was trachealess (trh), which encodes a bHLH-PAS domain transcription factor required for development of the trachea and other tubular organs. Trh activates expression of the fibroblast growth factor receptor Breathless, which, in turn, is required for directed migration of all tracheal branches. Using a combination of biochemical and transgenic approaches, we show that direct phosphorylation of Trh by PKB at serine 665 is essential for nuclear localization and functional activation of this regulator of branching morphogenesis.
Jin
J
J
Division of Cellular and Molecular Biology, Ontario Cancer Institute, University Health Network, Princess Margaret Hospital, Toronto, Ontario, M5G 2M9, Canada.
Anthopoulos
N
N
Wetsch
B
B
Binari
R C
RC
Isaac
D D
DD
Andrew
D J
DJ
Woodgett
J R
JR
Manoukian
A S
AS
D021581:Active Transport, Cell Nucleus / Q000502:physiology; D000818:Animals; D002460:Cell Line; D029721:Drosophila Proteins; D004331:Drosophila melanogaster / Q000196:embryology / Q000235:genetics / Q000502:physiology*; D005260:Female; D017930:Genes, Reporter; D006801:Humans; D008297:Male; D009024:Morphogenesis / Q000502:physiology; D010449:Peptide Mapping; D019869:Phosphatidylinositol 3-Kinases / Q000378:metabolism; D010766:Phosphorylation; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins / Q000235:genetics / Q000378:metabolism*; D051057:Proto-Oncogene Proteins c-akt; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction; D014132:Trachea / Q000033:anatomy & histology / Q000254:growth & development*; D014157:Transcription Factors / Q000235:genetics / Q000378:metabolism*
D029721:Drosophila Proteins; D019869:Phosphatidylinositol 3-Kinases; D017346:Protein Serine-Threonine Kinases; D011518:Proto-Oncogene Proteins; D051057:Proto-Oncogene Proteins c-akt; D011993:Recombinant Fusion Proteins; D014157:Transcription Factors; C099995:trh protein, Drosophila; C494918:AKT1 protein, human; C494917:Akt1 protein, Drosophila