Cited by 196Protein Kinase Regulation and GTPase SignalingReceptor Mechanisms and SignalingCellular transport and secretion

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The Phospholipase C Isozymes and Their Regulation

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Gresset, Aurelie, Sondek, John, Harden, T. Kendall·2012·Subcellular Biochemistry

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)P(2) to the Ca(2+)-mobilizing second messenger inositol(1,4,5)P(3) 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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Metadata

Authors
Gresset, A., Sondek, J., & Harden, T. K.
Affiliations
University of North Carolina at Chapel Hill (US)
Corresponding author
Harden, T. Kendall
Venue
Subcellular Biochemistry
Published
2012
Volume
58
Pages
61-94
ISSN
0306-0225 (ISSN-L)
OpenAlex
W199111168
Cited by
196
References
208
Citations by year
2026: 8 · 2025: 14 · 2024: 12 · 2023: 24 · 2022: 21 · 2021: 21 · 2020: 18 · 2019: 15 · 2018: 14 · 2017: 8 · 2016: 7 · 2015: 12 · 2014: 11 · 2013: 8 · 2012: 3
FWCI
18.57
Type
book chapter
Language
en
Open access
Locations
  • Sub-cellular biochemistry/Subcellular biochemistry (publishedVersion)
  • PubMed (publishedVersion)
  • Europe PMC (PubMed Central) (acceptedVersion)
  • PubMed Central (acceptedVersion)
Funders
National Institute of General Medical Sciences (R01GM057391)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Receptor Mechanisms and Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
Keywords
phospholipase C isozymes, inositol lipid signaling, phosphatidylinositol 4,5-bisphosphate, diacylglycerol, protein kinase C, heterotrimeric G proteins, tyrosine kinase phosphorylation, small GTPases, Ras, Rho, Rac, autoinhibition, catalytic core, calcium signaling
MeSH terms
Animals, Diglycerides, Enzyme Activation, Eukaryotic Cells, Gene Expression Regulation, Humans, Isoenzymes, Models, Molecular, Type C Phospholipases, Phosphorylation, Second Messenger Systems, Inositol 1,4,5-Trisphosphate, Protein Structure, Secondary, Protein Structure, Tertiary, Phosphatidylinositol 4,5-Diphosphate, Heterotrimeric GTP-Binding Proteins

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