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Molecular and Cellular Biology, January 2004, p. 796-808, Vol. 24, No. 2
0270-7306/04/$08.00+0     DOI: 10.1128/MCB.24.2.796-808.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.

Targeted Expression of the Class II Phosphoinositide 3-Kinase in Drosophila melanogaster Reveals Lipid Kinase-Dependent Effects on Patterning and Interactions with Receptor Signaling Pathways

Lindsay K. MacDougall,1* Mary Elizabeth Gagou,1 Sally J. Leevers,2 Ernst Hafen,3 and Michael D. Waterfield4,5

Biomolecular Sciences, University of Manchester Institute of Science and Technology, Manchester M60 1QD,1 Cancer Research UK, London WC2 3PX,2 Ludwig Institute for Cancer Research, Royal Free and University College Medical School, London W1W 7BS,4 Department of Biochemistry and Molecular Biology, University College London, London WC1E 6BT, United Kingdom,5 Zoologisches Institut, Universität Zürich, CH-8057 Zürich, Switzerland3

Received 18 July 2003/ Accepted 13 October 2003

Phosphoinositide 3-kinases (PI3Ks) can be divided into three distinct classes (I, II, and III) on the basis of their domain structures and the lipid signals that they generate. Functions have been assigned to the class I and class III enzymes but have not been established for the class II PI3Ks. We have obtained the first evidence for a biological function for a class II PI3K by expressing this enzyme during Drosophila melanogaster development and by using deficiencies that remove the endogenous gene. Wild-type and catalytically inactive PI3K_68D transgenes have opposite effects on the number of sensory bristles and on wing venation phenotypes induced by modified epidermal growth factor (EGF) receptor signaling. These results indicate that the endogenous PI3K_68D may act antagonistically to the EGF receptor-stimulated Ras-mitogen-activated protein kinase pathway and downstream of, or parallel to, the Notch receptor. A class II polyproline motif in PI3K_68D can bind the Drk adaptor protein in vitro, primarily via the N-terminal SH3 domain of Drk. Drk may thus be important for the localization of PI3K_68D, allowing it to modify signaling pathways downstream of cell surface receptors. The phenotypes obtained are markedly distinct from those generated by expression of the Drosophila class I PI3K, which affects growth but not pattern formation.

* Corresponding author. Mailing address: Biomolecular Sciences, UMIST, P.O. Box 88, Manchester M60 1QD, United Kingdom. Phone: 44 161 200 4222. Fax: 44 161 236 0409. E-mail: lindsay.macdougall{at}umist.ac.uk.

Molecular and Cellular Biology, January 2004, p. 796-808, Vol. 24, No. 2
0022-538X/04/$08.00+0     DOI: 10.1128/MCB.24.2.796-808.2004
Copyright © 2004, American Society for Microbiology. All Rights Reserved.



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