Phospholipase C is a key enzyme regulating intracellular calcium and modulating the phosphoinositide balance
Abstract
Spatial and temporal activation of phosphoinositide turnover enables eukaryotic cells to perform various functions such as cell proliferation/differentiation, fertilization, neuronal functions, and cell motility. In this system, phospholipase C (PLC) is a key enzyme, which hydrolyzes phosphatidylinositol 4,5-bisphosphate (PI(4,5)P(2)) into two second messengers, inositol 1,4,5-trisphosphate (Ins(1,4,5)P(3)) and diacylglycerol (DAG). Ins(1,4,5)P(3) triggers the release of calcium from intracellular stores, and DAG mediates the activation of protein kinase C (PKC). In parallel, PI(4,5)P(2) also directly regulates a variety of cellular functions, including cytoskeletal remodeling, cytokinesis, phagocytosis, membrane dynamics, and channel activity, in addition to its role as a substrate for PLC and phosphatidylinositol 3-kinase (PI3K), which generates PI(3,4,5)P(3). An imbalance of these phosphoinositides contributes to the pathogeneses of various human diseases. Therefore, strict regulation of the levels of PI(4,5)P(2) and PI(3,4,5)P(3) by PLC or other interconverting enzymes is necessary for cellular functions. In this review, we focus on the roles of PLC as a calcium-regulating enzyme and as a modulator of the phosphoinositide balance.
Integrity signals
Registry
Cites
Statistics
Claims the paper makes
Claims other papers make about this one
Each is checked against this paper’s own text: does it say what the citing paper says it does?
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 [31]
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 [31]
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 [31]
Cites
Phospholipase Cγ2 Is Essential in the Functions of B Cell and Several Fc Receptors
Wang, D., Feng, J., Wen, R., Marine, J.-C., Sangster, M. Y., Parganas, E., Hoffmeyer, A., Jackson, C. W., Cleveland, J. L., Murray, P. J., et al. (2000) · Immunity · doi:10.1016/s1074-7613(00)00005-4 · Cited by 475 · see citing works
Landman, N., Jeong, S. Y., Shin, S. Y., Voronov, S. V., Serban, G., Kang, M. S., Park, M. K., Di Paolo, G., Chung, S., & Kim, T.-W. (2006) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.0604954103 · Cited by 149 · see citing works
Phospholipase Cγ2 is necessary for separation of blood and lymphatic vasculature in mice
Ichise, H., Ichise, T., Ohtani, O., & Yoshida, N. (2009) · Development · doi:10.1242/dev.025353 · Cited by 98 · see citing works
Coupling Between B Cell Receptor and Phospholipase C-γ2 Is Essential for Mature B Cell Development
Hikida, M., Johmura, S., Hashimoto, A., Takezaki, M., & Kurosaki, T. (2003) · The Journal of Experimental Medicine · doi:10.1084/jem.20030280 · Cited by 62 · see citing works
Flagged first, then by citations
Cited by
Sorted by citations
P2X7 Interactions and Signaling – Making Head or Tail of It
Kopp, R., Krautloher, A., Ramírez-Fernández, A., & Nicke, A. (2019) · Frontiers in Molecular Neuroscience · doi:10.3389/fnmol.2019.00183 · Cited by 217 · see citing works
Kolczynska, K., Loza-Valdes, A., Hawro, I., & Sumara, G. (2020) · Lipids in Health and Disease · doi:10.1186/s12944-020-01286-8 · Cited by 199 · see citing works
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
- Authors
- Fukami, K., Inanobe, S., Kanemaru, K., & Nakamura, Y.
- Affiliations
- Tokyo University of Pharmacy and Life Sciences (JP)
- Corresponding author
- Fukami, Kiyoko
- Venue
- Progress in Lipid Research
- Publisher
- Elsevier BV
- Published
- 2010-10
- Volume
- 49
- Issue
- 4
- Pages
- 429-437
- ISSN
- 0163-7827 (ISSN-L)
- OpenAlex
- W2007949464
- Cited by
- 197
- References
- 4
- Citations by year
- 2026: 7 · 2025: 6 · 2024: 10 · 2023: 13 · 2022: 9 · 2021: 9 · 2020: 14 · 2019: 12 · 2018: 8 · 2017: 5 · 2016: 13 · 2015: 13 · 2014: 18 · 2013: 19 · 2012: 20
- FWCI
- 1.65
- Type
- journal article
- Language
- en
- Open access
- closed
- Locations
- Progress in Lipid Research (publishedVersion)
- PubMed (publishedVersion)
- Topics
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Physiology › Calcium signaling and nucleotide metabolism
- Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Sphingolipid Metabolism and Signaling
- Keywords
- phospholipase C, phosphatidylinositol 4,5-bisphosphate, phosphoinositide turnover, inositol 1,4,5-trisphosphate, diacylglycerol, intracellular calcium release, calcium signaling, protein kinase C, phosphatidylinositol 3,4,5-trisphosphate, phosphatidylinositol 3-kinase, second messengers
- MeSH terms
- Animals, Calcium, Cell Differentiation, Humans, Isoenzymes, Phosphatidylinositols, Type C Phospholipases, Tissue Distribution, Second Messenger Systems, Cell Proliferation
About these checks
Registry, retraction, Cites and statistics results are computed, not judged, with one exception: a printed reference that no index lists is read once by a model before it counts as a citation error. Claims are extracted by a model and kept only when their quote appears verbatim in the text; each cited source is then checked, with a model’s help, for whether it says what the claim relies on. Those verdicts can be wrong — read the claim’s quote and the cited source before relying on one.
Statistics and arithmetic are recomputed, not judged.
Confidence bands are shown only for fields calibrated on our annotated test set. None is calibrated yet, so no band is shown.
What counts as a claim ›How we measure confidence ›How we check this ›
Are you an author, or do you see a problem with this page? Request a review
