Phosphatidylinositol 5-phosphate 4-kinase (PIP4K) regulates TOR signaling and cell growth during Drosophila development

Amit Gupta, Sarah Toscano, Deepti Trivedi, David R. Jones, Swarna Mathre, Jonathan H. Clarke, Nullin Divecha, Padinjat Raghu

Research output: Contribution to journalArticlepeer-review

Abstract

During development, Drosophila larvae undergo a dramatic increase in body mass wherein nutritional and developmental cues are transduced into growth through the activity of complex signaling pathways. Class I phosphoinositide 3-kinases have an established role in this process. In this study we identify Drosophila phosphatidylinositol 5-phosphate 4-kinase (dPIP4K) as a phosphoinositide kinase that regulates growth during larval development. Loss-of-function mutants in dPIP4K show reduced body weight and prolonged larval development, whereas overexpression of dPIP4K results both in an increase in body weight and shortening of larval development. The growth defect associated with dPIP4K loss of function is accompanied by a reduction in the average cell size of larval endoreplicative tissues. Our findings reveal that these phenotypes are underpinned by changesin the signaling input into the target of rapamycin (TOR) signaling complex and changes in the activity of its direct downstream target p70 S6 kinase. Together, these results define dPIP4K activity as a regulator of cell growth and TOR signaling during larval development.
Original languageEnglish
Pages (from-to)5963-5968
Number of pages5
JournalProceedings of the National Academy of Sciences of the United States of America
Volume110
Issue number15
DOIs
Publication statusPublished - 9 Apr 2013

Research Beacons, Institutes and Platforms

  • Manchester Cancer Research Centre

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