ArticleeLife2019
Structural basis for the activation of PLC-γ isozymes by phosphorylation and cancer-associated mutations.
Article in eLife, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 66 papers, 1 of them a synthesis that pooled it.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
66 citing papers in PubMed, 1 synthesis or guideline pooled it, 59 citations in OpenAlex.
- Genome-wide analysis of genetic pleiotropy and causal genes across three age-related ocular disorders.Human genetics · 2023Pooled it
- LAT condensation gates PLCγ1 activation via bimodal LAT phosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Receptor tyrosine kinase signaling in mammalian eye development.Developmental biology · 2026Review
- Weak SLP-76/PLC-γ1 interaction fine-tunes T cell receptor signal strength to optimize T cell responsiveness.Nature communications · 2026Article
- Optogenetic control of PLC-γ1 activity directs cell motility.The Journal of cell biology · 2026Article
- Impaired cortical actin dynamics via lanosterol-dependent HMG-CoA reductase downregulation mediates IFN-α-induced mast cell stabilization.The Journal of biological chemistry · 2026Article
- Structural insights into Phospholipase Cε activity and regulation.The Journal of biological chemistry · 2026Review
- PLCG2 signaling and genetic resilience in Alzheimer's disease.Molecular neurodegeneration · 2026Review
- Biochemical Reconstitution and FRAP Analysis of Membrane-Associated Condensates on Supported Lipid Bilayers.Bio-protocol · 2026Article
- Insulin Resistance and Inflammation.International journal of molecular sciences · 2026Review
- Concurrence of FGFR1 mutations modulates oncogenesis in glioneuronal tumors.The EMBO journal · 2025Article
- Medial prefrontal cortex circuit dynamics involved in stage-specific addiction.Brain structure & function · 2025Review
- Characterisation of an allosteric site in PLCγ enzymes and implications for development of their specific inhibitors.The Biochemical journal · 2025Article
- Optogenetic control of PLC-γ1 activity polarizes cell motility.bioRxiv : the preprint server for biology · 2025Article
- Weak SLP-76-PLC-γ1 interaction in the LAT-nucleated multi-protein complex fine-tunes TCR signal strength to optimize T cell responsiveness.bioRxiv : the preprint server for biology · 2025Article
- Hyperactive PLCG1 induces cell-autonomous and bystander T cell activation and drug resistance.EMBO reports · 2025Article
- Heterozygous variants ineLife · 2025Article
- FGF-induced phospholipase Cγ signaling regulates lacrimal gland branching by competing with PI3K in phosphoinositide metabolism.Cell reports · 2025Article
- Tau from SPAM Transgenic Mice Exhibit Potent Strain-Specific Prion-Like Seeding Properties Characteristic of Human Neurodegenerative Diseases.Neuromolecular medicine · 2025Article
- Purification and characterization of full-length monomeric TEC family kinase, ITK.Protein expression and purification · 2025Article
6 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
8 authors at 1 institution in 1 country.
Funding
Abstract
Direct activation of the human phospholipase C-γ isozymes (PLC-γ1, -γ2) by tyrosine phosphorylation is fundamental to the control of diverse biological processes, including chemotaxis, platelet aggregation, and adaptive immunity. In turn, aberrant activation of PLC-γ1 and PLC-γ2 is implicated in inflammation, autoimmunity, and cancer. Although structures of isolated domains from PLC-γ isozymes are available, these structures are insufficient to define how release of basal autoinhibition is coupled to phosphorylation-dependent enzyme activation. Here, we describe the first high-resolution structure of a full-length PLC-γ isozyme and use it to underpin a detailed model of their membrane-dependent regulation. Notably, an interlinked set of regulatory domains integrates basal autoinhibition, tyrosine kinase engagement, and additional scaffolding functions with the phosphorylation-dependent, allosteric control of phospholipase activation. The model also explains why mutant forms of the PLC-γ isozymes found in several cancers have a wide spectrum of activities, and highlights how these activities are tuned during disease.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.