The lipid products of phosphoinositide 3-kinase increase cell motility through protein kinase C

Melanie P. Derman, Alex Toker, John H. Hartwig, Katherine Spokes, J R Falck, Ching Shih Chen, Lewis C. Cantley, Lloyd G. Cantley

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Abstract

Phosphoinositide 3-kinase has been implicated as an activator of cell motility in a variety of recent studies, yet the role of its lipid product, phosphatidylinositol 1,4,5-trisphosphate (PtdIns-3,4,5-P3), has yet to be elucidated. In this study, three independent preparations of PtdIns-3,4,5- P3 were found to increase the motility of NIH 3T3 cells when examined utilizing a microchemotaxis chamber. Dipalmitoyl L-α-phosphatidyl-D-myo- inositol 3,4,5-triphosphate (Di-C16-PtdIns-3,4,5-P3) also produced actin reorganization and membrane ruffling. Cells pretreated with 12-O- tetradecanoylphorbol-13-acetate to cause down-regulation of protein kinase C (PKC) exhibited complete inhibition of cell motility induced by Di-C16- PtdIns-3,4,5-P3. These results are consistent with previous observations that PtdIns-3,4,5-P3 activates Ca2+-independent PKC isoforms in vitro and in vivo and provide the first demonstration of an in vivo role for the lipid products of the phosphoinositide 3-kinase. PtdIns-3,4,5-P3 appears to directly initiate cellular motility via activation of a PKC family member.

Original languageEnglish (US)
Pages (from-to)6465-6470
Number of pages6
JournalJournal of Biological Chemistry
Volume272
Issue number10
DOIs
Publication statusPublished - Mar 7 1997

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ASJC Scopus subject areas

  • Biochemistry

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