Formation and Metabolism of Inositol Phosphates: The Inositol Tris/Tetrakisphosphate Pathway

  • John R. Williamson
  • Carl A. Hansen
  • Roy A. Johanson
  • Kathleen E. Coll
  • Michael Williamson
Part of the Advances in Experimental Medicine and Biology book series (AEMB, volume 232)


Many cell functions are modulated by receptor-activated mechanisms that act by increasing the free Ca2+ concentration in the cytosol (Williamson et al, 1981; Rasmussen and Barrett, 1984). Calcium mediates its effects by causing activity changes of a variety of proteins, including protein kinases, either directly or after binding to calmodulin or other Ca2+ -binding proteins (Cohen, 1985). A large number of studies have now established that a wide range of compounds, including hormones, secretagogues, neurotransmitters, chemoattractants and other cell activating subtances that involve Ca2+ mobilization, cause an activation of a phosphodiesterase (phospholipase C), which breaks down inositol lipids in the plasma membrane (Berridge and Irvine, 1984; Williamson et al., 1985; Hokin, 1985; Downes and Michell, 1985). However, unlike receptor-mediated activation of adenylate cyclase, which produces cAMP as the only second messenger, receptor-mediated inositol lipid breakdown serves a dual-signalling role with production of two second messengers having different functions. One of these compounds, myoinositol 1,4,5-trisphosphate (Ins(l,4,5)P3), is responsible for eliciting intracellular Ca2+ mobilization (Berridge and Irvine, 1984; Williamson, 1986), while the second compound, 1,2-diacylglycerol (DAG), has as its primary signalling role the activation of protein kinase C (Nishizuka, 1986). Hence in principle agents that interact with inositol lipid metabolism not only cause Ca2+ release with phosphorylation of proteins by Ca2+ -dependent protein kinases but also phosphorylation of a different set of proteins by activation of protein kinase C. However, most of these latter proteins have not been functionally characterized, and presently it is not clear whether receptor-mediated activation of protein kinase C via DAG production has as its physiological mode of action on cell function a synergistic role with Ca2 or a negative feedback modulatory role (Williamson and Hansen, 1987). Probably both effects occur, depending on the cell type and the extent to which protein kinase C becomes activated (Nishizuka, 1986).


Inositol Phosphate Phosphomonoesterase Activity Inositol Lipid Inositol Phosphate Product Muscarinic Receptor Stimulation 
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Copyright information

© Plenum Press, New York 1988

Authors and Affiliations

  • John R. Williamson
    • 1
  • Carl A. Hansen
    • 1
  • Roy A. Johanson
    • 1
  • Kathleen E. Coll
    • 1
  • Michael Williamson
    • 1
  1. 1.Department of Biochemistry and BiophysicsUniversity of PennsylvaniaPennsylvaniaUSA

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