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

Research output: Contribution to journalArticle

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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
StatePublished - Mar 7 1997

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Molecular Motor Proteins
1-Phosphatidylinositol 4-Kinase
Phosphatidylinositols
Protein Kinase C
Cell Movement
Phosphotransferases
Lipids
NIH 3T3 Cells
Tetradecanoylphorbol Acetate
phosphatidylinositol 3,4,5-triphosphate
Actins
Protein Isoforms
Acetates
Demonstrations
Down-Regulation
Chemical activation
Cells
Membranes

ASJC Scopus subject areas

  • Biochemistry

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The lipid products of phosphoinositide 3-kinase increase cell motility through protein kinase C. / Derman, Melanie P.; Toker, Alex; Hartwig, John H.; Spokes, Katherine; Falck, J R; Chen, Ching Shih; Cantley, Lewis C.; Cantley, Lloyd G.

In: Journal of Biological Chemistry, Vol. 272, No. 10, 07.03.1997, p. 6465-6470.

Research output: Contribution to journalArticle

Derman, MP, Toker, A, Hartwig, JH, Spokes, K, Falck, JR, Chen, CS, Cantley, LC & Cantley, LG 1997, 'The lipid products of phosphoinositide 3-kinase increase cell motility through protein kinase C', Journal of Biological Chemistry, vol. 272, no. 10, pp. 6465-6470. https://doi.org/10.1074/jbc.272.10.6465
Derman, Melanie P. ; Toker, Alex ; Hartwig, John H. ; Spokes, Katherine ; Falck, J R ; Chen, Ching Shih ; Cantley, Lewis C. ; Cantley, Lloyd G. / The lipid products of phosphoinositide 3-kinase increase cell motility through protein kinase C. In: Journal of Biological Chemistry. 1997 ; Vol. 272, No. 10. pp. 6465-6470.
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