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© The Rockefeller University Press, 0021-9525/2000//627 $5.00
The Journal of Cell Biology, Volume 150, Number 3, , 2000 627-642

Restructuring of Focal Adhesion Plaques by Pi 3-Kinase

: Regulation by Ptdins (3,4,5-P)₃ Binding to -Actinin

Jeffrey A. Greenwood^a, Anne B. Theibert^b, Glenn D. Prestwich^c, and Joanne E. Murphy-Ullrich^a

^a Department of Pathology, Division of Molecular and Cellular Pathology,
^b Department of Neurobiology, University of Alabama at Birmingham, Birmingham, Alabama 35294
^c Department of Medicinal Chemistry, University of Utah, Salt Lake City, Utah 84112
Department of Biochemistry and Biophysics, 2103B Agricultural and Life Sciences, Oregon State University, Corvallis, OR 97331-7305.(541) 737-0481(541) 737-4997

jeffrey.greenwood{at}orst.edu

Focal adhesions are an elaborate network of interconnecting proteins linking actin stress fibers to the extracellular matrix substrate. Modulation of the focal adhesion plaque provides a mechanism for the regulation of cellular adhesive strength. Using interference reflection microscopy, we found that activation of phosphoinositide 3-kinase (PI 3-kinase) by PDGF induces the dissipation of focal adhesions. Loss of this close apposition between the cell membrane and the extracellular matrix coincided with a redistribution of -actinin and vinculin from the focal adhesion complex to the Triton X-100–soluble fraction. In contrast, talin and paxillin remained localized to focal adhesions, suggesting that activation of PI 3-kinase induced a restructuring of the plaque rather than complete dispersion. Furthermore, phosphatidylinositol (3,4,5)-trisphosphate (PtdIns (3,4,5)-P₃), a lipid product of PI 3-kinase, was sufficient to induce restructuring of the focal adhesion plaque. We also found that PtdIns (3,4,5)-P₃ binds to -actinin in PDGF-treated cells. Further evidence demonstrated that activation of PI 3-kinase by PDGF induced a decrease in the association of -actinin with the integrin β subunit, and that PtdIns (3,4,5)-P₃ could disrupt this interaction in vitro. Modification of focal adhesion structure by PI 3-kinase and its lipid product, PtdIns (3,4,5)-P₃, has important implications for the regulation of cellular adhesive strength and motility.

Key Words: cell motility • phosphoinositide 3-kinase • PDGF • integrin • vinculin

© 2000 The Rockefeller University Press

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