Regulation of Drosophila Tracheal System Development by Protein Kinase B

Jing Jin; Norman Anthopoulos; Benjamin Wetsch; Richard C. Binari; Daniel D. Isaac; Deborah J. Andrew; James R. Woodgett; Armen S. Manoukian

doi:10.1016/S1534-5807(01)00090-9

Regulation of Drosophila Tracheal System Development by Protein Kinase B

Jing Jin, Norman Anthopoulos, Benjamin Wetsch, Richard C. Binari, Daniel D. Isaac, Deborah J. Andrew, James R. Woodgett, Armen S. Manoukian

School of Medicine

Research output: Contribution to journal › Article › peer-review

31 Scopus citations

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)
Pages (from-to)	817-827
Number of pages	11
Journal	Developmental Cell
Volume	1
Issue number	6
DOIs	https://doi.org/10.1016/S1534-5807(01)00090-9
State	Published - Dec 2001

ASJC Scopus subject areas

Molecular Biology
General Biochemistry, Genetics and Molecular Biology
Developmental Biology
Cell Biology

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10.1016/S1534-5807(01)00090-9

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title = "Regulation of Drosophila Tracheal System Development by Protein Kinase B",

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.",

author = "Jing Jin and Norman Anthopoulos and Benjamin Wetsch and Binari, {Richard C.} and Isaac, {Daniel D.} and Andrew, {Deborah J.} and Woodgett, {James R.} and Manoukian, {Armen S.}",

note = "Funding Information: 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.",

year = "2001",

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doi = "10.1016/S1534-5807(01)00090-9",

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T1 - Regulation of Drosophila Tracheal System Development by Protein Kinase B

AU - Jin, Jing

AU - Anthopoulos, Norman

AU - Wetsch, Benjamin

AU - Binari, Richard C.

AU - Isaac, Daniel D.

AU - Andrew, Deborah J.

AU - Woodgett, James R.

AU - Manoukian, Armen S.

N1 - Funding Information: 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.

PY - 2001/12

Y1 - 2001/12

N2 - 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.

AB - 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.

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Regulation of Drosophila Tracheal System Development by Protein Kinase B

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