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Phosphatidylinositol 3-Kinase and Its Novel Product, Phosphatidylinositol 3-phosphate, Are Present in Saccharomyces cerevisiae*

  • K.R. Auger
    Correspondence
    To whom correspondence should be addressed.
    Affiliations
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111

    Dept. of Physiology, Tufts University School of Medicine, 136 Harrison Ave., Boston, MA 02111. Tel.: 617-956-6744. Fax: 617-956-0445
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  • C.L. Carpenter
    Affiliations
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111

    Hematology-Oncology Unit, Massachusetts General Hospital, Boston, Massachusetts 02114
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  • L.C. Cantley
    Affiliations
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111
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  • L Varticovski
    Affiliations
    Department of Physiology, Tufts University School of Medicine, Boston, Massachusetts 02111
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  • Author Footnotes
    * This research was supported by National Institutes of Health Grant GM 36624. The costs of publication of this article were defrayed in part by the payment of page charges. This article must therefore be hereby marked “advertisement” in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.
Open AccessPublished:December 05, 1989DOI:https://doi.org/10.1016/S0021-9258(19)47043-9
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      The metabolism of polyphosphoinositides has been shown to be an important factor in controlling the proliferation of Saccharomyces cerevisiae. The monophosphate form of phosphatidylinositol has been assumed to be phosphatidylinositol 4-phosphate (PI-4-P). Recent evidence from our laboratory has established that a phosphatidylinositol (PI) kinase, which phosphorylates the D-3 position of the inositol ring (PI 3-kinase), is associated with many activated proteintyrosine kinases and may play an important role in the signaling of cell proliferation (Auger, K. R., Serunian, L. A., Soltoff, S. P., Libby, P., and Cantley, L. C. (1989) Cell 57, 167-175). To determine the evolutionary conservation of this enzymatic activity, we investigated its presence in yeast. In vitro PI kinase assays of yeast cell homogenates demonstrated that PI 3-kinase activity was present. Preliminary biochemical characterization of the activity suggested that it was quite different from the mammalian enzyme yet catalyzed the same reaction, i.e. phosphorylating the D-3 hydroxyl position of the inositol ring of phosphatidyl-myo-inositol. [3H]Inositol labeling of intact yeast cells with the subsequent extraction, deacylation, and high performance liquid chromatography analysis of the lipids demonstrated that PI-3-P was as abundant as the PI-4-P isomer. The conservation of this enzymatic activity from yeast to man suggests that it has an important functional role in the cell cycle.

      REFERENCES

        • Whitman M.
        • Cantley L.
        Biochim. Biophys. Acta. 1988; 948: 327-344
        • Fleischman L.F.
        • Cantley L.
        Am. J. Physiol. 1988; 255: C531-C535
        • Uno I.
        • Fukami K.
        • Kato H.
        • Takenawa T.
        • Ishikawa T.
        Nature. 1988; 333: 188-190
        • Whitman M.
        • Kaplan D.
        • Roberts T.
        • Cantley L.
        Biochem. J. 1987; 247: 165-174
        • Whitman M.
        • Downes C.P.
        • Keeler M.
        • Keller T.
        • Cantley L.
        Nature. 1988; 332: 644-646
        • Kaplan D.R.
        • Whitman M.
        • Schaffhausen B.
        • Pallas D.C.
        • White M.
        • Cantley L.
        • Roberts T.M.
        Cell. 1987; 50: 1021-1029
        • Auger K.R.
        • Serunian L.A.
        • Soltoff S.P.
        • Libby P.
        • Cantley L.C.
        Cell. 1989; 57: 167-175
        • Traynor-Kaplan A.E.
        • Harris A.L.
        • Thompson B.L.
        • Taylor P.
        • Sklar L.A.
        Nature. 1988; 334: 353-356
        • Nikawa J.
        • Kodake T.
        • Yamashita S.
        J. Biol. Chem. 1987; 262: 4876-4881
        • Whitman M.
        • Kaplan D.R.
        • Schaffhausen B.
        • Cantley L.
        • Roberts T.M.
        Nature. 1985; 315: 239-242
        • Holland K.M.
        • Homann M.J.
        • Belunis C.J.
        • Carman G.M.
        J. Bacteriol. 1988; 170: 828-833
        • Stephens L.
        • Hawkins P.T.
        • Downes C.P.
        Biochem. J. 1989; 259: 267-276
        • Kaibuchi K.
        • Miyajima A.
        • Arai K.
        • Matsumoto K.
        Proc. Natl. Acad. Sci. U. S. A. 1986; 83: 8172-8176
        • Dahl J.S.
        • Dahl C.E.
        Biochem. Biophys. Res. Commun. 1985; 133: 844-850
        • Toda T.
        • Uno I.
        • Ishikawa T.
        • Powers S.
        • Kataoka T.
        • Broek D.
        • Cameron S.
        • Broach J.
        • Matsumoto K.
        • Wigler M.
        Cell. 1985; 40: 27-36
        • Kato H.
        • Uno I.
        • Ishikawa T.
        • Takenawa T.
        J. Biol. Chem. 1989; 264: 3116-3121
        • Tanaka S.
        • Hasegawa S.
        • Hishinuma F.
        • Kurata S.
        Cell. 1989; 57: 675-681
        • Belunis C.J.
        • Bae-Lee M.
        • Kelley M.J.
        • Carman G.M.
        J. Biol. Chem. 1988; 263: 18897-18903
        • Serunian L.A.
        • Haber M.T.
        • Fukui T.
        • Kim J.W.
        • Rhee S.G.
        • Lowenstein J.M.
        • Cantley L.C.
        J. Biol. Chem. 1989; 264: 17809-17815
        • Lips D.L.
        • Majerus P.W.
        • Gorga F.R.
        • Young A.T.
        • Benjamin T.L.
        J. Biol. Chem. 1989; 264: 8759-8763