Phosphoinositides and Cell Growth

  • William J. Wasilenko
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 321)

Abstract

Phosphoinositides are a class of membrane phospholipids that serve as precursors to the important second messengers inositol(1,4,5)P3 and diacylglycerol, which mediate the release of intracellular calcium and the activation of protein kinase C, respectively.1,2 The key event in the production of these signals is the hydrolysis of phoshatidylinositol(4,5)P2 by phospholipase C. This traditional pathway of signal transduction is utilized by activated receptors for a variety of diverse stimuli, including hormones, growth factors, neurotransmitters and chemotactic factors. Recently, several new pathways of phosphoinositide (PI) metabolism have been discovered in cells stimulated by growth factors or transformed by certain oncogene products.1,3 These new pathways branch off the classical routes of PI hydrolysis and appear to be linked to poorly understood events in cellular regulation that are distinct from calcium release and C-kinase activation. In this discussion, several of these new aspects of PI metabolism relating to cell transformation will be illustrated, and a model for neoplastic transformation by the src tyrosine kinase oncogene, will be presented.

Keywords

Hydrolysis HPLC Tyrosine Sarcoma Thrombin 

Preview

Unable to display preview. Download preview PDF.

Unable to display preview. Download preview PDF.

References

  1. 1.
    M.J. Berridge and R.F. Irvine, Inositol phosphates and cell signalling, Nature. 341:197–205 (1989).PubMedCrossRefGoogle Scholar
  2. 2.
    V.S. Bansal and P.W. Majerus, Phosphatidylinositol-derived precursors and signals, Annu. Rev. Cell Biol. 6:41–67 (1990).PubMedCrossRefGoogle Scholar
  3. 3.
    L.C. Cantley, K.R. Auger, C. Carpenter, B. Duckworth, A. Graziani, R. Kapeller, and S. Soltoff, Oncogenes and signal transduction, Cell. 64:281–302 (1991).PubMedCrossRefGoogle Scholar
  4. 4.
    B.J. Drucker, H.J. Mamon, and T.M. Roberts, Oncogenes, growth factors and signal transduction, N Eng J Med. 321:1383–91 (1989).CrossRefGoogle Scholar
  5. 5.
    J.T. Parsons and M.J. Weber, Genetics of SrC: structure and functional organization of a protein tyrosine kinase, Curr Top Microbiol Immunol. 147:80–127 (1989).Google Scholar
  6. 6.
    C.A. Koch, D. Anderson, M.F. Moran, C. Ellis, and T. Pawson, SH2 and SH3 domains: Elements that control interactions of cytoplasmic signaling proteins, Science. 252: 668–74. (1991)PubMedCrossRefGoogle Scholar
  7. 7.
    I.G. Macara, Oncogenes and cellular signal transduction, Physiol Rev. 69: 797–820. (1989)PubMedGoogle Scholar
  8. 8.
    Y. Sugimoto, M. Whitman, L.C. Cantley, and R.L. Erikson, Evidence that the Rous sarcoma virus transforming gene product phosphorylates phospatidylinositol and diacyglyccrol, Proc Natl Acad Sci USA. 81:2117–21 (1984).PubMedCrossRefGoogle Scholar
  9. 9.
    R.M. Johnson, W.J. Wasilenko, R.R. Mattingly, M.J. Weber, and J.C. Garrison, Fibroblasts transformed with v-src show enhanced formation of an inositol tetrakisphosphate, Science. 246: 121–24 (1989).PubMedCrossRefGoogle Scholar
  10. 10.
    R.R. Mattingly, L.R. Stephens, R.F. Irvine, and J.C. Garrison, Effects of transformation with the v-src oncogene on inositol phosphate metabolism in rat-I cells: d-myo-inositol 1,4,5,6-tetrakisphosphate is increased in v-src transformed fibroblasts and can be synthesized from d-myo-inositol 1,3,4-trisphosphate in cytosolic extracts, J Biol Chem. 266:15144–53 (1991).PubMedGoogle Scholar
  11. 11.
    M. Whitman, D. Kaplan, T. Roberts, and L. Cantley, Evidence for two distinct phosphatidylinositol kinases in fibroblasts: implications for cellular transformation, Biochem J. 247:165–74 (1987).PubMedGoogle Scholar
  12. 12.
    M. Whitman, C.P. Downes, T. Keeler, T. Keller, and L. Cantley, Type 1 phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate, Nature. 332: 644–46 (1988).PubMedCrossRefGoogle Scholar
  13. 13.
    M. Otsu, I. Hiles, I. Gout, M.J. Fry, F. Ruiz-Larrea, G. Panayotou, A. Thompson, R. Dhand, et. al, Characterization of two 85kD. proteins that associate with receptor tyrosine kinases, middle-T/pp60c-src complexes, and PI3-kinase, Cell. 65:91–104 (1991).PubMedCrossRefGoogle Scholar
  14. 14.
    L.R. Stephens, P.T. Hawkins, N. Carter, S.B. Chawala, A.J. Morris, et al, L-myo-inositol 1,4,5,6-tetrakisphosphate is present in both mammalian and avian cells, Biochem J. 249:271–82 (1988).PubMedGoogle Scholar
  15. 15.
    F.S. Menniti, K.G. Oliver, K. Nogimori, J.F. Obie, S. Shears, and J.W. Putney Jr., Origins of myo-inositol tetrakisphosphates in agonist-stimulated rat pancreatoma cells. Stimulation by bombesin of myoinositol 1,3,4,5,6-pentakisphosphate to myo-inositol 3,4,5,6-tetrakisphosphate, J Biol Chem. 265: 11167–76 (1990).PubMedGoogle Scholar
  16. 16.
    T. Balla, L. Hunyady, A.J. Baukal, and K.J. Catt, Structures and metabolism of inositol tetrakisphosphates and inositol pentakisphosphates in bovine adrenal glomerulosa cells, J Biol Chem. 264: 9386–90 (1989).PubMedGoogle Scholar
  17. 17.
    P. Grondin, M. Plantavid, C. Sultan, et.al, Interaction of p60c-src, phospholipase C. inositol-lipid and diacylglycerol with the cytoskeletons of thrombin-stimulated platelets. J Biol Chem. 266: 15705–09 (1991).PubMedGoogle Scholar
  18. 18.
    A. Sjolander, K. Yamamoto, B.E. Huber, and E.G. Lapetina, Association of p21ras with phosphatidylinositol 3-kinase, J Biol Chem. 88:7908–12 (1991).Google Scholar

Copyright information

© Springer Science+Business Media New York 1992

Authors and Affiliations

  • William J. Wasilenko
    • 1
  1. 1.Head and Neck Tumor Biology Program, Depts. Microbiology/Immunology & Otolaryngology Head and Neck SurgeryEastern Virginia Medical SchoolNorfolkUSA

Personalised recommendations