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The Phospholipase C Isozymes and Their Regulation
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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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“In mammals, PLC enzymes that use phosphoinositides (preferentially PI(4,5)P2) as their substrates have been grouped into six families (β, γ, δ, ε, ζ and η).”
From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [30]
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“Overall, the signalling connectivity remains best defined for the G-protein coupled receptors (GPCRs) and PLCβ isoforms, mediated by the α and βγ subunits of G-proteins, and for the RTKs and tyrosine kinases linked to immunoreceptor tyrosine-based activation motif (ITAM)-associated receptors, that activate PLC enzymes by direct phosphorylation.”
From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [30]
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“Within each family are multiple members: four PLCβ (1–4), two PLCγ (1 and 2), three PLCδ (1, 3, 4), one PLCε, one PLCζ and two PLCη (1 and 2) making thirteen PLCs in total (reviewed in [27–33]) (Figure 3A).”
From Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane (2020) · cites this paper as [30]
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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
- ORCID
- Sondek, John
- Venue
- Subcellular Biochemistry
- Publisher
- Springer Netherlands
- Published
- 2012
- Volume
- 58
- Pages
- 61-94
- ISSN
- 0306-0225 (ISSN-L)
- PMC
- PMC3638883
- 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
- green
- europepmc.org
- 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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