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Cited by 89Protein Kinase Regulation and GTPase SignalingPI3K/AKT/mTOR signaling in cancerSphingolipid Metabolism and Signaling

Phospholipase C families: Common themes and versatility in physiology and pathology

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Katan, Matilda, Cockcroft, Shamshad·2020·Progress in Lipid Research
DOI 10.1016/j.plipres.2020.101065
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Abstract

Phosphoinositide-specific phospholipase Cs (PLCs) are expressed in all mammalian cells and play critical roles in signal transduction. To obtain a comprehensive understanding of these enzymes in physiology and pathology, a detailed structural, biochemical, cell biological and genetic information is required. In this review, we cover all these aspects to summarize current knowledge of the entire superfamily. The families of PLCs have expanded from 13 enzymes to 16 with the identification of the atypical PLCs in the human genome. Recent structural insights highlight the common themes that cover not only the substrate catalysis but also the mechanisms of activation. This involves the release of autoinhibitory interactions that, in the absence of stimulation, maintain classical PLC enzymes in their inactive forms. Studies of individual PLCs provide a rich repertoire of PLC function in different physiologies. Furthermore, the genetic studies discovered numerous mutated and rare variants of PLC enzymes and their link to human disease development, greatly expanding our understanding of their roles in diverse pathologies. Notably, substantial evidence now supports involvement of different PLC isoforms in the development of specific cancer types, immune disorders and neurodegeneration. These advances will stimulate the generation of new drugs that target PLC enzymes, and will therefore open new possibilities for treatment of a number of diseases where current therapies remain ineffective.

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Authors
Katan, M., & Cockcroft, S.
Affiliations
  • Institute of Structural and Molecular Biology (GB)
  • University College London (GB)
Corresponding author
Cockcroft, Shamshad
ORCID
Venue
Progress in Lipid Research
Publisher
Elsevier BV
Published
2020-11
Volume
80
Pages
101065
ISSN
0163-7827 (ISSN-L)
DOI
10.1016/j.plipres.2020.101065
OpenAlex
W3088889248
Cited by
89
References
486
Citations by year
2026: 7 · 2025: 20 · 2024: 17 · 2023: 21 · 2022: 14 · 2021: 10
FWCI
1.08
Type
journal article
Language
en
Open access
Licence
Locations
  • Progress in Lipid Research (publishedVersion)
  • PubMed (publishedVersion)
  • UCL Discovery (University College London) (submittedVersion)
Funders
Biotechnology and Biological Sciences Research Council
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 isoforms, signal transduction, enzyme structure, autoinhibition, cancer, immune disorders, neurodegeneration
MeSH terms
Protein Domains, Animals, Humans, Neoplasms, Type C Phospholipases, Signal Transduction, High-Throughput Screening Assays

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