Amplification of Ca2+ Signaling by Diacylglycerol-mediated Inositol 1,4,5-Trisphosphate Production*

Stimulation of various cell surface receptors leads to the production of inositol 1,4,5-trisphosphate (IP3) and diacylglycerol (DAG) through phospholipase C (PLC) activation, and the IP3 and DAG in turn trigger Ca2+ release through IP3 receptors and protein kinase C activation, respectively. The amount of IP3 produced is particularly critical to determining the spatio-temporally coordinated Ca2+-signaling patterns. In this paper, we report a novel signal cross-talk between DAG and the IP3-mediated Ca2+-signaling pathway. We found that a DAG derivative, 1-oleoyl-2-acyl-sn-glycerol (OAG), induces Ca2+ oscillation in various types of cells independently of protein kinase C activity and extracellular Ca2+. The OAG-induced Ca2+ oscillation was completely abolished by depletion of Ca2+ stores or inhibition of PLC and IP3 receptors, indicating that OAG stimulates IP3 production through PLC activation and thereby induces IP3-induced Ca2+ release. Furthermore, intracellular accumulation of endogenous DAG by a DAG-lipase inhibitor greatly increased the number of cells responding to agonist stimulation at low doses. These results suggest a novel physiological function of DAG, i.e. amplification of Ca2+ signaling by enhancing IP3 production via its positive feedback effect on PLC activity.

• Publication year

  2005

• Venue

  Journal of Biological Chemistry

• Publication date

  2005-03-25

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/JBC.M409535200PMID 15637078
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

• PKC-independent inhibition of neuronal nicotinic acetylcholine receptors by diacylglycerol.

  2004cited by this paper
• The families of kinases removing the Ca2+ releasing second messenger Ins(1,4,5)P3.

  2004cited by this paper
• Transient Receptor Potential Channel Activation Causes a Novel Form of [Ca 2+]i Oscillations and Is Not Involved in Capacitative Ca 2+ Entry in Glial Cells

  2003cited by this paper
• The TRPC3/6/7 subfamily of cation channels.

  2003cited by this paper
• A Novel Recombinant Hyperaffinity Inositol 1,4,5-Trisphosphate (IP3) Absorbent Traps IP3, Resulting in Specific Inhibition of IP3-mediated Calcium Signaling*

  2002cited by this paper
• Activation of phospholipase Cgamma2 by tyrosine phosphorylation.

  2002cited by this paper
• Cellular Regulation of RGS Proteins: Modulators and Integrators of G Protein Signaling

  2002cited by this paper
• The cellular and molecular basis of store-operated calcium entry

  2002cited by this paper
• Structure, regulation, and function of phospholipase C isozymes.

  2002cited by this paper
• The organisation and functions of local Ca(2+) signals.

  2001cited by this paper
• Regulation of G proteins by covalent modification

  2001cited by this paper
• Phospholipase C(epsilon): a novel Ras effector.

  2001cited by this paper
• Muscarinic acetylcholine receptor regulation of TRP6 Ca2+ channel isoforms. Molecular structures and functional characterization.

  2001cited by this paper
• Regulation of phosphoinositide-specific phospholipase C.

  2001cited by this paper
• Structure, function, and control of phosphoinositide-specific phospholipase C.

  2000cited by this paper
• Mechanism of Inhibition of Cyclic Nucleotide–Gated Ion Channels by Diacylglycerol

  2000cited by this paper
• Signal transduction. The calcium entry pas de deux.

  2000cited by this paper
• Function and regulation of sarcoplasmic reticulum Ca2+-ATPase: advances during the past decade and prospects for the coming decade.

  2000cited by this paper
• Molecular mechanism of the inhibition of phospholipase C beta 3 by protein kinase C.

  2000cited by this paper
• Molecular and Functional Characterization of a Novel Mouse Transient Receptor Potential Protein Homologue TRP7

  1999cited by this paper
• Molecular properties of inositol 1,4,5-trisphosphate receptors.

  1999cited by this paper
• Sarco/endoplasmic reticulum Ca2+ (SERCA)-pumps: link to heart beats and calcium waves.

  1999cited by this paper
• Expression of inositol trisphosphate receptors.

  1999cited by this paper
• Calmodulin mediates calcium-dependent inactivation of the cerebellar type 1 inositol 1,4,5-trisphosphate receptor.

  1999cited by this paper
• Calcium signalling.

  1999cited by this paper
• Direct activation of human TRPC6 and TRPC3 channels by diacylglycerol

  1999cited by this paper
• RasGRP, a Ras guanyl nucleotide- releasing protein with calcium- and diacylglycerol-binding motifs.

  1998cited by this paper
• Calcium - a life and death signal

  1998cited by this paper
• 2APB, 2-aminoethoxydiphenyl borate, a membrane-penetrable modulator of Ins(1,4,5)P3-induced Ca2+ release.

  1997cited by this paper
• Activation of the G protein Gq/11 through tyrosine phosphorylation of the alpha subunit.

  1997cited by this paper
• Diacylglycerol analogs inhibit the rod cGMP-gated channel by a phosphorylation-independent mechanism.

  1995cited by this paper
• Growth factor upregulation of a phosphoinositide-coupled metabotropic glutamate receptor in cortical astrocytes

  1995cited by this paper
• In vitro tyrosine phosphorylation of PLC-gamma 1 and PLC-gamma 2 by src-family protein tyrosine kinases.

  1993cited by this paper
• Increase of the catalytic activity of phospholipase C-gamma 1 by tyrosine phosphorylation.

  1990cited by this paper
• Inositol polyphosphates and intracellular calcium release.

  1989cited by this paper
• Inositol phosphates and cell signalling

  1989cited by this paper
• Effect of harvesting methods, growth conditions and growth phase on diacylglycerol levels in cultured human adherent cells.

  1988cited by this paper
• Molecular model for receptor-stimulated calcium spiking.

  1988cited by this paper
• Down regulation of protein kinase C in neuronal cells: effects on neurotransmitter release

  1987cited by this paper
• Quantitative measurement of sn-1,2-diacylglycerols present in platelets, hepatocytes, and ras- and sis-transformed normal rat kidney cells.

  1986cited by this paper
• A new generation of Ca2+ indicators with greatly improved fluorescence properties.

  1985cited by this paper

• Neuroregulation of histamine of circadian rhythm disorder induced by chronic intermittent hypoxia.

  2025cites this paper
• Single-cell sequencing and organoids: applications in organ development and disease

  2025cites this paper
• Progress and Prospects of Research on the Role of Phosphatidic Acid in Response to Adverse Stress in Plants

  2025cites this paper
• Thermosensory Roles of G Protein‐Coupled Receptors and Other Cellular Factors in Animals

  2024cites this paper
• Insights on Platelet-Derived Growth Factor Receptor α-Positive Interstitial Cells in the Male Reproductive Tract

  2024cites this paper
• Sophorolipid inhibits histamine-induced itch by decreasing PLC/IP3R signaling pathway activation and modulating TRPV1 activity

  2023cites this paper
• Comparison between Sickle Cell Disease Patients and Healthy Donors: Untargeted Lipidomic Study of Erythrocytes

  2023cites this paper
• Impact of schizophrenia GWAS loci converge onto distinct pathways in cortical interneurons vs glutamatergic neurons during development

  2022cites this paper
• Association Between Variants in Calcineurin Inhibitor Pharmacokinetic and Pharmacodynamic Genes and Renal Dysfunction in Adult Heart Transplant Recipients

  2021cites this paper
• Emerging Roles of Calcium Signaling in the Development of Non-Alcoholic Fatty Liver Disease

  2021cites this paper
• Advances in Intracellular Calcium Signaling Reveal Untapped Targets for Cancer Therapy

  2021cites this paper
• Melatonin Inhibits Osteoclastogenesis and Osteolytic Bone Metastasis: Implications for Osteoporosis

  2021influential citation
• A mathematical model of intricate calcium dynamics and modulation of calcium signalling by mitochondria in pancreatic acinar cells

  2021cites this paper
• Quercetin inhibits histamine-induced calcium influx in human keratinocyte via histamine H4 receptors.

  2021cites this paper
• The Signaling Pathways Involved in the Anticonvulsive Effects of the Adenosine A1 Receptor

  2020cites this paper
• Role of IP3 Receptors in Shaping the Carotid Chemoreceptor Response to Hypoxia But Not to Hypercapnia in the Rat Carotid Body: An Evidence Review.

  2020cites this paper
• Phosphoinositide-specific phospholipase C isoforms are conveyed by osteosarcoma-derived extracellular vesicles

  2020cites this paper
• Nonlinear Dynamic Modeling of 2-Dimensional Interdependent Calcium and Inositol 1,4,5-Trisphosphate in Cardiac Myocyte

  2019cites this paper
• Different expression and localization of Phosphoinositide specific Phospholipases C in human osteoblasts, osteosarcoma cell lines, Ewing Sarcoma and Synovial Sarcoma.

  2017cites this paper
• A novel function of TLR4 in mediating the immunomodulatory effect of Benzanthrone, an environmental pollutant.

  2017cites this paper
• LPS, Oleuropein and Blueberry extracts affect the survival, morphology and Phosphoinositide signalling in stimulated human endothelial cells

  2017cites this paper
• Mechanical Strain Regulates Osteoblast Proliferation Through Ca2+-CaMK-CREB Signal Pathway.

  2016cites this paper
• Comparison of Phosphoinositide-Specific Phospholipase C Expression Panels of Human Osteoblasts Versus MG-63 and Saos Osteoblast-Like Cells

  2016cites this paper
• U-73122 reduces the cell growth in cultured MG-63 ostesarcoma cell line involving Phosphoinositide-specific Phospholipases C

  2016cites this paper
• The role of Phospholipase C enzymes in health and disease

  2015cites this paper
• Metabolic regulation of the ultradian oscillator Hes1 by reactive oxygen species.

  2015cites this paper
• Ezrin-related Phosphoinositide pathway modifies RhoA and Rac1 in human osteosarcoma cell lines

  2015cites this paper
• Impairment and reorganization of the phosphoinositide-specific phospholipase C enzymes in suicide brains.

  2015cites this paper
• Fibroblast growth factor acts upon the transcription of phospholipase C genes in human umbilical vein endothelial cells

  2014cites this paper
• Neuropeptide Y reduces the expression of PLCB2, PLCD1 and selected PLC genes in cultured human endothelial cells

  2014cites this paper
• Prostaglandins and Other Lipid Mediators nterleukin-1 inhibits synthesis of 5-lipooxygenase in ipopolysaccharide-stimulated equine whole blood

  2014cites this paper
• The role of HuD, a post-transcriptional regulator, in the development and function of the murine neocortex

  2014cites this paper
• Ezrin silencing remodulates the expression of Phosphoinositide-specific Phospholipase C enzymes in human osteosarcoma cell lines

  2014cites this paper
• Phospholipids Signaling System in Plant Innate Immunity

  2014cites this paper
• Development of an organotypic 3D in vitro model of normal human breast tissue : a tool for cancer initiation studies

  2014cites this paper
• Phospholipase D1 Increases Bcl-2 Expression During Neuronal Differentiation of Rat Neural Stem Cells

  2014cites this paper
• Characterisation of novel lipids generated by activated human platelets via COX-1

  2013cites this paper
• Expression of Phosphoinositide-Specific Phospholipase C Enzymes in Human Skin Fibroblasts

  2013cites this paper
• Immunoglobulins G from patients with sporadic amyotrophic lateral sclerosis affects cytosolic Ca2+ homeostasis in cultured rat astrocytes.

  2013cites this paper
• Lypopolysaccharide Downregulates the Expression of Selected Phospholipase C Genes in Cultured Endothelial Cells

  2013cites this paper
• THE REGULATION AND PACKAGING OF SYNAPTIC VESICLES RELATED TO RECRUITMENT WITHIN CRAYFISH AND FRUIT FLY NEUROMUSCULAR JUNCTIONS: VARIATIONS IN LOW- AND HIGH-OUTPUT TERMINALS

  2013cites this paper
• Expression of phosphoinositide-specific phospholipase C enzymes in normal endometrium and in endometriosis.

  2012cites this paper
• Serotonin and Synaptic Transmission at Invertebrate Neuromuscular Junctions

  2012cites this paper
• Phosphoinositide pathway and the signal transduction network in neural development

  2012cites this paper
• Modeling the Contributions of Ca2+ Flows to Spontaneous Ca2+ Oscillations and Cortical Spreading Depression-Triggered Ca2+ Waves in Astrocyte Networks

  2012cites this paper
• Phosphoinositide pathway and the signal transduction network in neural development

  2012cites this paper
• Diacylglycerol Signaling Underlies Astrocytic ATP Release

  2011cites this paper
• Alteration of Ceramide Synthase 6/C16-Ceramide Induces Activating Transcription Factor 6-mediated Endoplasmic Reticulum (ER) Stress and Apoptosis via Perturbation of Cellular Ca2+ and ER/Golgi Membrane Network*

  2011cites this paper
• Deletion of PLCB1 gene in schizophrenia-affected patients

  2011cites this paper
• 1p36.32 rearrangements and the role of PI-PLC η2 in nervous tumours

  2011cites this paper
• Expression of phosphoinositide-specific phospholipase C isoforms in human umbilical vein endothelial cells

  2011cites this paper
• O-Silylated C3-halohydrins as a novel class of protected building blocks for total, regio- and stereocontrolled synthesis of glycerolipid frameworks.

  2010cites this paper
• GABAA and GABAB receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of intracellular Ca2+

  2010cites this paper
• Expression of phosphoinositide‐specific phospholipase C isoenzymes in cultured astrocytes activated after stimulation with lipopolysaccharide

  2010cites this paper
• GABA A and GABA B receptors of distinct properties affect oppositely the proliferation of mouse embryonic stem cells through synergistic elevation of

  2010cites this paper
• Signalling in the genomic era

  2010cites this paper
• Knockdown of stromal interaction molecule 1 attenuates hepatocyte growth factor-induced endothelial progenitor cell proliferation

  2010cites this paper
• The virucidal properties of silver ion-exchange resins and metal-based nanoparticles and their potential use in water purification

  2010cites this paper
• Signalling in the genomic era

  2010cites this paper
• Expression pattern and sub‐cellular distribution of phosphoinositide specific phospholipase C enzymes after treatment with U‐73122 in rat astrocytoma cells

  2010cites this paper
• Pain and learning in a spinal system: contradictory outcomes from common origins.

  2009cites this paper
• Effect of Organ Culture on Noradrenaline- Evoked Contraction, Calcium Signalling and TRPC Expression in Rat Mesenteric Artery

  2009cites this paper
• Effects of siRNA knock-down of TRPC6 and InsP(3)R1 in vasopressin-induced Ca(2+) oscillations of A7r5 vascular smooth muscle cells.

  2008cites this paper
• Membranes: a meeting point for lipids, proteins and therapies

  2008cites this paper
• Systems biology perspectives on calcium signaling and DNA repair

  2008cites this paper
• Prostanoids induce egr1 gene expression in cementoblastic OCCM cells.

  2007cites this paper
• Defective chemoattractant-induced calcium signalling in S100A9 null neutrophils.

  2007cites this paper
• Expression of phosphoinositide‐specific phospholipase C isoenzymes in cultured astrocytes

  2007cites this paper
• The IP3 receptor/Ca2+ channel and its cellular function.

  2007cites this paper
• IP3 receptor/Ca2+ channel: from discovery to new signaling concepts

  2007cites this paper
• Differential coupling of the P2Y1 receptor to Galpha14 and Galphaq/11 proteins during the development of the rat salivary gland.

  2006cites this paper
• Differential coupling of the P2Y1 receptor to Gα14 and Gαq/11 proteins during the development of the rat salivary gland

  2006cites this paper
• Characterization of the Arabidopsis Calcineurin B-like Calcium Sensors in Environmental and Developmental Signal Transduction

  2006cites this paper
• Neutrophil function in S100A9 null mice.

  2006cites this paper
• Calcium signaling in non‐excitable cells: Ca2+ release and influx are independent events linked to two plasma membrane Ca2+ entry channels

  2006cites this paper
• IRBIT suppresses IP3 receptor activity by competing with IP3 for the common binding site on the IP3 receptor.

  2006cites this paper
• Insights on TRP channels from in vivo studies in Drosophila.

  2006cites this paper
• Models of IP3 and Ca2+ oscillations: frequency encoding and identification of underlying feedbacks.

  2006cites this paper