Regulation and physiological functions of mammalian phospholipase C
Abstract
Phospholipase C (PLC) is a key enzyme in phosphoinositide metabolism. PLC hydrolyses phosphatidylinositol 4,5-bis-phosphate to generate two second messengers, inositol 1,4,5-trisphosphate and diacylglycerol, that generate diverse cellular responses. PLC is activated by various signalling molecules, including Ca2+, heterometric G proteins, small G proteins, and receptor/non-receptor tyrosine kinases. In addition to their enzymatic activity, some PLC subtypes also function as a guanine nucleotide exchange factor, GTPase-activating protein, and adaptor protein, independent of their lipase activity. There are 13 PLC isozymes in mammals, and they are categorized into six classes based on structure. Generation and analysis of genetically modified mice has revealed the unexpectedly diverse physiological functions of PLC isozymes. Although all PLC isozymes catalyze the same reaction, each PLC isozyme has unique physiological functions. This review focuses on the regulation and physiological functions of PLCs.
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There are thirteen PLCs in mammals: four PLCβ, two PLCγ, three PLCδ, one PLCε, one PLCζ and two PLCη.
“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 [28]
Mammalian PLC enzymes that use phosphoinositides, preferentially PI(4,5)P2, are grouped into six families (β, γ, δ, ε, ζ and η).
“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 [28]
Signalling connectivity is best defined for GPCRs and PLCβ isoforms via G-protein α and βγ subunits, and for RTKs and tyrosine kinases linked to ITAM-associated receptors that activate PLC enzymes by direct phosphorylation.
“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 [28]
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Phosphatidylinositol(4,5)bisphosphate: diverse functions at the plasma membrane
Katan, M., & Cockcroft, S. (2020) · Essays in Biochemistry · doi:10.1042/ebc20200041 · Cited by 176 · see citing works
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- Authors
- Nakamura, Y., & Fukami, K.
- Affiliations
- Tokyo University of Pharmacy and Life Sciences (JP)
- Corresponding author
- Fukami, Kiyoko
- Venue
- Journal of Biochemistry
- Publisher
- Oxford University Press (OUP)
- Published
- 2017-01-27
- Volume
- 161
- Issue
- 4
- Pages
- mvw094
- ISSN
- 0021-924X (ISSN-L)
- 1756-2651
- OpenAlex
- W2581941142
- Cited by
- 122
- References
- 5
- Citations by year
- 2026: 2 · 2025: 9 · 2024: 10 · 2023: 21 · 2022: 10 · 2021: 19 · 2020: 26 · 2019: 15 · 2018: 6 · 2017: 4
- FWCI
- 5.69
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- The Journal of Biochemistry (publishedVersion)
- PubMed (publishedVersion)
- Funders
- Uehara Memorial Foundation
- Japan Society for the Promotion of Science (26440036)
- 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 › PI3K/AKT/mTOR signaling in cancer
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Keywords
- phospholipase C, PLC isozymes, phosphoinositide metabolism, phosphatidylinositol 4,5-bisphosphate, inositol 1,4,5-trisphosphate, diacylglycerol, second messengers, G proteins, small GTPases, tyrosine kinase, guanine nucleotide exchange factor, GTPase-activating protein, adaptor proteins, physiological function
- MeSH terms
- Animals, Diglycerides, Humans, Isoenzymes, Type C Phospholipases, Inositol 1,4,5-Trisphosphate, Gene Expression Regulation, Enzymologic, Phosphatidylinositol 4,5-Diphosphate, Guanine Nucleotide Exchange Factors, GTPase-Activating Proteins
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