The class II phosphoinositide 3-kinase PI3K-C2β regulates cell migration by a PtdIns(3)P dependent mechanism
The biological and pathophysiological significance of class II phosphoinositide 3‐kinase enzyme expression currently remains unclear. Using an in vitro scrape wound assay and time‐lapse video microscopy, we demonstrate that cell motility is increased in cultures expressing recombinant PI3K‐C2β enzym...
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Published in | Journal of cellular physiology Vol. 205; no. 3; pp. 452 - 462 |
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Main Authors | , , , , , , , |
Format | Journal Article |
Language | English |
Published |
Hoboken
Wiley Subscription Services, Inc., A Wiley Company
01.12.2005
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Online Access | Get full text |
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Summary: | The biological and pathophysiological significance of class II phosphoinositide 3‐kinase enzyme expression currently remains unclear. Using an in vitro scrape wound assay and time‐lapse video microscopy, we demonstrate that cell motility is increased in cultures expressing recombinant PI3K‐C2β enzyme. In addition, overexpression of PI3K‐C2β transiently decreased cell adhesion, stimulated the formation of cytoplasmic processes, and decreased the rate of cell proliferation. Consistent with these observations, expression of PI3K‐C2β also decreased expression of alpha4 beta1 integrin subunits. Using asynchronous cultures, we show that endogenous PI3K‐C2β is present in lamellipodia of motile cells. When cells expressing recombinant PI3K‐C2β were plated onto fibronectin, cortical actin staining increased markedly and actin rich lamellipodia and filopodia became evident. Overexpression of a 2xFYVEHrs domain fusion protein abolished this response demonstrating that the effect of PI3K‐C2β on the reorganization of actin filaments is dependent upon PtdIns(3)P. Finally, overexpression of PI3K‐C2β increased GTP loading of Cdc42. Our data demonstrates for the first time, that PI3K‐C2β plays a regulatory role in cell motility and that the mechanism by which it reorganizes the actin cytoskeleton is dependent upon PtdIns(3)P production. © 2005 Wiley‐Liss, Inc. |
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Bibliography: | NKRF - No. RP28/2/01 BBSRC - No. C14810 ark:/67375/WNG-8BQ8MKNW-3 Wellcome Trust - No. 058558 ArticleID:JCP20478 istex:E31262FD57065E89578BA3BB8C8994EBF48DD9A7 |
ISSN: | 0021-9541 1097-4652 |
DOI: | 10.1002/jcp.20478 |