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The Phospholipase C Isozymes and Their Regulation

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Book cover Phosphoinositides I: Enzymes of Synthesis and Degradation

Part of the book series: Subcellular Biochemistry ((SCBI,volume 58))

Abstract

The physiological effects of many extracellular neurotransmitters, hormones, growth factors, and other stimuli are mediated by receptor-promoted activation of phospholipase C (PLC) and consequential activation of inositol lipid signaling pathways. These signaling responses include the classically described conversion of phosphatidylinositol(4,5)P2 to the Ca2+-mobilizing second messenger inositol(1,4,5)P3 and the protein kinase C-activating second messenger diacylglycerol as well as alterations in membrane association or activity of many proteins that harbor phosphoinositide binding domains. The 13 mammalian PLCs elaborate a minimal catalytic core typified by PLC-d to confer multiple modes of regulation of lipase activity. PLC-b isozymes are activated by Gaq- and Gbg-subunits of heterotrimeric G proteins, and activation of PLC-g isozymes occurs through phosphorylation promoted by receptor and non-receptor tyrosine kinases. PLC-e and certain members of the PLC-b and PLC-g subclasses of isozymes are activated by direct binding of small G proteins of the Ras, Rho, and Rac subfamilies of GTPases. Recent high resolution three dimensional structures together with biochemical studies have illustrated that the X/Y linker region of the catalytic core mediates autoinhibition of most if not all PLC isozymes. Activation occurs as a consequence of removal of this autoinhibition.

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  1. Department of Pharmacology, University of North Carolina School of Medicine, 27599, Chapel Hill, NC, USA

    Aurelie Gresset, John Sondek & T. Kendall Harden

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  1. , NICHD, National Institutes of Health, Convent Drive 49, Bethesda, 20892-4480, Maryland, USA

    Tamas Balla

  2. , Cancer- and Immunobiology, University of Basel, Mattenstrasse 28, Basel, 4058, Switzerland

    Matthias Wymann

  3. , Pharmacology and Cancer Biology, Duke University Medical Center, Durham, 27710, North Carolina, USA

    John D. York

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Gresset, A., Sondek, J., Harden, T. (2012). The Phospholipase C Isozymes and Their Regulation. In: Balla, T., Wymann, M., York, J. (eds) Phosphoinositides I: Enzymes of Synthesis and Degradation. Subcellular Biochemistry, vol 58. Springer, Dordrecht. https://doi.org/10.1007/978-94-007-3012-0_3

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