Specific requirement for the p85-p110α phosphatidylinositol 3-kinase during epidermal growth factor-stimulated actin nucleation in breast cancer cells

Karen Hill, Susan Welti, Jinghua Yu, James T. Murray, Shu Chin Yip, John S. Condeelis, Jeffrey E. Segall, Jonathan M. Backer

Research output: Contribution to journalArticle

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Abstract

We have studied the role of phosphatidylinositol 3-kinases (PI 3- kinases) in the regulation of the actin cytoskeleton in MTLn3 rat adenocarcinoma cells. Stimulation of MTLn3 cells with epidermal growth factor (EGF) induced a rapid increase in actin polymerization, with production of lamellipodia within 3 min. EGF-stimulated lamellipodia were blocked by 100 nM wortmannin, suggesting the involvement of a class Ia PI 3-kinase. MTLn3 cells contain equal amounts of p110α and p110β, and do not contain p110δ. Injection of specific inhibitory antibodies to p110α induced cell rounding and blocked EGF-stimulated lamellipod extension, whereas control or anti- p110β antibodies had no effect. In contrast, both antibodies inhibited EGF- stimulated DNA synthesis. An in situ assay for actin nucleation showed that EGF-stimulated formation of new barbed ends was blocked by injection of anti- p110α antibodies. In summary, the p110α isoform of PI 3-kinase is specifically required for EGF-stimulated actin nucleation during lamellipod extension in breast cancer cells.

Original languageEnglish (US)
Pages (from-to)3741-3744
Number of pages4
JournalJournal of Biological Chemistry
Volume275
Issue number6
DOIs
StatePublished - Feb 11 2000

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Phosphatidylinositols
Phosphatidylinositol 3-Kinases
Epidermal Growth Factor
Actins
Nucleation
Cells
Breast Neoplasms
Pseudopodia
Antibodies
Anti-Idiotypic Antibodies
Injections
Actin Cytoskeleton
Polymerization
Rats
Assays
Protein Isoforms
Adenocarcinoma
DNA

ASJC Scopus subject areas

  • Biochemistry

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Specific requirement for the p85-p110α phosphatidylinositol 3-kinase during epidermal growth factor-stimulated actin nucleation in breast cancer cells. / Hill, Karen; Welti, Susan; Yu, Jinghua; Murray, James T.; Yip, Shu Chin; Condeelis, John S.; Segall, Jeffrey E.; Backer, Jonathan M.

In: Journal of Biological Chemistry, Vol. 275, No. 6, 11.02.2000, p. 3741-3744.

Research output: Contribution to journalArticle

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AU - Condeelis, John S.

AU - Segall, Jeffrey E.

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