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PI 3-Kinase and Receptor-Linked Signal Transduction

  • Chapter
Lipid Second Messengers

Part of the book series: Handbook of Lipid Research ((HLRE,volume 8))

Abstract

Classical phosphoinositide (PI) metabolism leading to the well-known second messengers diacylglycerol (DAG) and inositol-1,4,5-trisphosphate (InsP3), was elucidated more than 10 years ago (Fig. 4-1A). Many mitogenic signals stimulate PI turnover and transformed cells have constitutively activated PI turnover. It was work on this classical pathway that eventually led to the discovery of the novel PI pathway. Let us first look briefly at the classical pathway, in which phosphatidylinositol (Ptdlns) is phosphorylated by PtdIns 4-kinase to PtdIns-4-P, which is subsequently phosphorylated by PtdIns-4-P 5-kinase to form PtdIns-4,5-P2. Much of the PtdIns-4,5-P2 in the cell is found on the inner leaflet of the plasma membrane. This lipid can serve as a substrate for PI-specific phospholipase C (PLC), liberating DAG and IP3. IP3 is a water-soluble molecule which, when released into the cytosol, acts to liberate intracellular stores of Ca2+, increasing the intracellular concentration of Ca2+ from the resting level of ~110 nM to 400–1000 nM, which in turn can activate a number of Ca2+-sensitive enzymes and channels. The DAG released from Ptdlns-4,5-P2 remains in the membrane and serves as a cofactor in activating many of the protein kinase C (PKC) isotypes.

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Authors and Affiliations

  1. Department of Physiology, Tufts University, Massachusetts, Boston, 02111, USA

    Brian C. Duckworth

  2. Division of Signal Transduction, Beth Israel Hospital, and Department of Cell Biology, Harvard Medical School, Boston, Massachusetts, 02115, USA

    Lewis C. Cantley

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  1. Brian C. Duckworth
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  2. Lewis C. Cantley
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Editors and Affiliations

  1. Department of Biochemistry, Duke University Medical Center, 27710, Durham, North Carolina, USA

    Robert M. Bell

  2. Glaxo Wellcome, Inc., Research Triangle Park, North Carolina, USA

    Robert M. Bell

  3. Howard Hughes Medical Institute and Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, 37232, Nashville, Tennessee, USA

    John H. Exton

  4. Departments of Medicine and Biochemistry, the Nora Eccles Harrison Cardiovascular Research and Training Institute, and the Eccles Institute of Human Genetics, University of Utah School of Medicine, 84112, Salt Lake City, Utah, USA

    Stephen M. Prescott

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© 1996 Springer Science+Business Media New York

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Duckworth, B.C., Cantley, L.C. (1996). PI 3-Kinase and Receptor-Linked Signal Transduction. In: Bell, R.M., Exton, J.H., Prescott, S.M. (eds) Lipid Second Messengers. Handbook of Lipid Research, vol 8. Springer, Boston, MA. https://doi.org/10.1007/978-1-4899-1361-6_4

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  • DOI: https://doi.org/10.1007/978-1-4899-1361-6_4

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