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Molecular and Cellular Biology, July 2008, p. 4549-4561, Vol. 28, No. 14
0270-7306/08/$08.00+0 doi:10.1128/MCB.00150-08
Copyright © 2008, American Society for Microbiology. All Rights Reserved.

Department of Biochemistry, Microbiology, and Immunology, University of Ottawa, 451 Smyth Road, Ottawa, Ontario, Canada K1H 8M5
Received 21 January 2008/ Returned for modification 4 March 2008/ Accepted 5 May 2008
Eukaryotic elongation factor 1 alpha 2 (eEF1A2) is a transforming gene product that is highly expressed in human tumors of the ovary, lung, and breast. eEF1A2 also stimulates actin remodeling, and the expression of this factor is sufficient to induce the formation of filopodia, long cellular processes composed of bundles of parallel actin filaments. Here, we find that eEF1A2 stimulates formation of filopodia by increasing the cellular abundance of cytosolic and plasma membrane-bound phosphatidylinositol-4,5 bisphosphate [PI(4,5)P2]. We have previously reported that the eEF1A2 protein binds and activates phosphatidylinositol-4 kinase III beta (PI4KIIIβ), and we find that production of eEF1A2-dependent PI(4,5)P2 and generation of filopodia require PI4KIIIβ. Furthermore, PI4KIIIβ is itself capable of activating both the production of PI(4,5)P2 and the creation of filopodia. We propose a model for extrusion of filopodia in which eEF1A2 activates PI4KIIIβ, and activated PI4KIIIβ stimulates production of PI(4,5)P2 and filopodia by increasing PI4P abundance. Our work suggests an important role for both eEF1A2 and PI4KIIIβ in the control of PI(4,5)P2 signaling and actin remodeling.
Published ahead of print on 12 May 2008.
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