The class II phosphoinositide 3‐kinase PI3K‐C2β regulates cell migration by a PtdIns(3)P dependent mechanism

Publisher Website
Google Scholar
Abstract
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.