Abstract
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.
Original language | English (US) |
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Pages (from-to) | 817-827 |
Number of pages | 11 |
Journal | Developmental Cell |
Volume | 1 |
Issue number | 6 |
DOIs | |
State | Published - Dec 2001 |
Funding
We thank S. Leevers, T. Xu, and B.-Z. Shilo for fly stocks. We also thank K. Saigo for his kind gift of tgo cDNA and DNA for the B-123 btl enhancer element. M. Krasnow kindly provided MAb2A12 and btl cDNA. We also thank S. Scanga, R. Fernandez, M. Birnbaum, B. Calvieri, S. Leevers, and R. Gupta for helpful advice and support. Also, this study was greatly enhanced through comments of anonymous reviewers. This work was supported by grants from the National Cancer Institute of Canada to A.S.M. and J.R.W., as well as by a collaborative research grant from Kinetek Pharmaceuticals Inc. (Vancouver) and by NIH grant RO1 DE12873 to D.J.A.
ASJC Scopus subject areas
- Molecular Biology
- General Biochemistry, Genetics and Molecular Biology
- Developmental Biology
- Cell Biology