ArticleCurrent biology : CB2010
Synergistic activation of phospholipase C-beta3 by Galpha(q) and Gbetagamma describes a simple two-state coincidence detector.
Article in Current biology : CB, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 46 papers.
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Who cites it
46 citing papers in PubMed.
- An integrated mechanism of GProceedings of the National Academy of Sciences of the United States of America · 2025Article
- RGS2 is an innate immune checkpoint for suppressing Gαq-mediated IFNγ generation and lung injury.iScience · 2025Article
- Light-sensitive CaProceedings of the National Academy of Sciences of the United States of America · 2024Article
- Biasing GMolecular pharmacology · 2024Article
- Synaptic plasticity via receptor tyrosine kinase/G-protein-coupled receptor crosstalk.Cell reports · 2024Article
- The mechanism ofProceedings of the National Academy of Sciences of the United States of America · 2023Article
- Article
- Endogenous μ-opioid-Neuropeptide Y Y1 receptor synergy silences chronic postoperative pain in mice.PNAS nexus · 2023Article
- Activation Mechanisms and Diverse Functions of Mammalian Phospholipase C.Biomolecules · 2023Review
- Article
- Bioinformatics analysis of lncRNA-related ceRNA networks in the peripheral blood lymphocytes of Kazakh patients with essential hypertension in Xinjiang.Frontiers in cardiovascular medicine · 2023Article
- Molecular regulation of PLCβ signaling.Methods in enzymology · 2023Review
- Coincident Regulation of PLCMolecular pharmacology · 2022Article
- Glucosylsphingosine evokes pruritus via activation of 5-HTBritish journal of pharmacology · 2022Article
- The calcineurin regulator Sarah enables distinct forms of homeostatic plasticity at theFrontiers in synaptic neuroscience · 2022Article
- G-Protein Coupled Receptors (GPCRs): Signaling Pathways, Characterization, and Functions in Insect Physiology and Toxicology.International journal of molecular sciences · 2021Review
- Structure and regulation of phospholipase Cβ and ε at the membrane.Chemistry and physics of lipids · 2021Review
- Regulation of bifunctional proteins in cells: Lessons from the phospholipase Cβ/G protein pathway.Protein science : a publication of the Protein Society · 2020Review
- Review
- Maintenance of homeostatic plasticity at theeLife · 2019Article
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Authors and funding
5 authors.
Funding
Abstract
backgroundReceptors that couple to G(i) and G(q) often interact synergistically in cells to elicit cytosolic Ca(2+) transients that are several-fold higher than the sum of those driven by each receptor alone. Such synergism is commonly assumed to be complex, requiring regulatory interaction between components, multiple pathways, or multiple states of the target protein.
resultsWe show that cellular G(i)-G(q) synergism derives from direct supra-additive stimulation of phospholipase C-beta3 (PLC-beta3) by G protein subunits Gbetagamma and Galpha(q), the relevant components of the G(i) and G(q) signaling pathways. No additional pathway or proteins are required. Synergism is quantitatively explained by the classical and simple two-state (inactive<-->active) allosteric mechanism. We show generally that synergistic activation of a two-state enzyme reflects enhanced conversion to the active state when both ligands are bound, not merely the enhancement of ligand affinity predicted by positive cooperativity. The two-state mechanism also explains why synergism is unique to PLC-beta3 among the four PLC-beta isoforms and, in general, why one enzyme may respond synergistically to two activators while another does not. Expression of synergism demands that an enzyme display low basal activity in the absence of ligand and becomes significant only when basal activity is </= 0.1% of maximal.
conclusionsSynergism can be explained by a simple and general mechanism, and such a mechanism sets parameters for its occurrence. Any two-state enzyme is predicted to respond synergistically to multiple activating ligands if, but only if, its basal activity is strongly suppressed.
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