Multiple roles of phosphoinositide-specific phospholipase C isozymes
Open accessAbstract
Phosphoinositide-specific phospholipase C is an effector molecule in the signal transduction process. It generates two second messengers, inositol-1,4,5-trisphosphate and diacylglycerol from phosphatidylinositol 4,5-bisphosphate. Currently, thirteen mammal PLC isozymes have been identified, and they are divided into six groups: PLC-beta, -gamma, -delta, -epsilon, -zeta and -eta. Sequence analysis studies demonstrated that each isozyme has more than one alternative splicing variant. PLC isozymes contain the X and Y domains that are responsible for catalytic activity. Several other domains including the PH domain, the C2 domain and EF hand motifs are involved in various biological functions of PLC isozymes as signaling proteins. The distribution of PLC isozymes is tissue and organ specific. Recent studies on isolated cells and knockout mice depleted of PLC isozymes have revealed their distinct phenotypes. Given the specificity in distribution and cellular localization, it is clear that each PLC isozyme bears a unique function in the modulation of physiological responses. In this review, we discuss the structural organization, enzymatic properties and molecular diversity of PLC splicing variants and study functional and physiological roles of each isozyme.
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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 [29]
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 [29]
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 [29]
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Self-citation
- Authors
- Suh, P.-G., Park, J.-I., Manzoli, L., Cocco, L., Peak, J. C., Katan, M., Fukami, K., Kataoka, T., Yun, S.-U., & Ryu, S.-H.
- Affiliations
- Pohang University of Science and Technology (KR)
- University of Bologna (IT)
- Institute of Cancer Research (GB)
- Tokyo University of Pharmacy and Life Sciences (JP)
- Kobe University (JP)
- ORCID
- Venue
- BMB Reports
- Published
- 2008-06-30
- Volume
- 41
- Issue
- 6
- Pages
- 415-434
- ISSN
- 1976-6696 (ISSN-L)
- OpenAlex
- W2116903886
- Cited by
- 501
- References
- 5
- Citations by year
- 2026: 6 · 2025: 18 · 2024: 17 · 2023: 27 · 2022: 21 · 2021: 20 · 2020: 25 · 2019: 24 · 2018: 18 · 2017: 27 · 2016: 28 · 2015: 23 · 2014: 30 · 2013: 43 · 2012: 64
- FWCI
- 2.80
- Type
- journal article
- Language
- en
- Open access
- gold
- doi.org
- Licence
- cc-by-nc
- Locations
- BMB Reports (publishedVersion, cc-by-nc)
- PubMed (publishedVersion)
- Archivio istituzionale della ricerca (Alma Mater Studiorum Università di Bologna) (submittedVersion, cc-by-nc)
- UCL Discovery (University College London) (submittedVersion)
- Open Access System for Information Sharing (Pohang University of Science and Technology) (submittedVersion)
- Scholarworks@UNIST (Ulsan National Institute of Science and Technology) (submittedVersion)
- Funders
- Pohang University of Science and Technology
- Korea Science and Engineering Foundation
- Ministry of Education and Human Resources Development
- 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
- phosphatidylinositol-specific phospholipase C, PLC isozymes, phospholipase C beta, phospholipase C-gamma, alternative splicing isoforms, inositol 1,4,5-trisphosphate, diacylglycerol, phosphatidylinositol 4,5-bisphosphate, signal transduction, pleckstrin homology domain, C2 domain, EF-hand motifs, tissue-specific gene expression, knockout mice
- MeSH terms
- Animals, Humans, Isoenzymes, Alternative Splicing, Mice, Knockout, Catalytic Domain, Mice, Phosphoinositide Phospholipase C
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