PathwaysCGMPPathwaySynthaseNucleotidesIntracellularProteinCGASGuanosineNucleotideGuanylate cyclase activityMotilityProteinsDegradationCalciumReceptorSecond messengersDiguanylateRegulationPseudomonasInnateSynthesisImmuneCascadesMechanismsSTINGEukaryotesAccumulationAmplifyReceptorsEnzymesInflammatoryOverexpressionGene expressionIncreasesVitroContrastCellsTRIFTransient
Pathways9
- Signal-transduction pathways follow a broadly similar course that can be viewed as a molecular circuit. (axonmedchem.com)
- 1] Signal-Transduction Pathways: An Introduction to Information Metabolism. (axonmedchem.com)
- We examined the role of cGMP-dependent signaling pathways and intracellular Ca(2+)stores in mediating the positive chronotropic effect of NO donors. (ox.ac.uk)
- Her Ph.D. thesis research, which identified intercellular and intracellular signaling pathways required for neural network dynamics within the mammalian circadian clock, was carried out in the laboratory of Dr. Erik Herzog at Washington University in St. Louis. (nih.gov)
- It is likely to act as a bioactive compound by exerting reactive oxygen species (ROS)-scavenging activity and/or binding to specific proteins such as oxidative enzymes and transcriptional factors in signal transduction pathways. (rsc.org)
- Here, I review recent studies on potential molecular mechanisms and signal transduction pathways for P. aeruginosa surface sensing. (brad.ac.uk)
- Binding of various FGFs to FGFR3 induces receptor dimerization and transphosphorylation of tyrosine residues [ 9 ], leading to activation of several downstream signaling pathways, including mitogen-activated protein kinase (MAPK) cascades ( Fig. 1 ) [ 10 , 11 ]. (e-apem.org)
- Chronically high insulin levels may disrupt the close apposition of β-adrenergic receptors and PKA, identifying a new mechanism for crosstalk between heterologous signal transduction pathways. (nature.com)
- He has over 12 years of experience in the field of innate immunity with specific expertise in Toll-like receptor (TLR), inflammasome and cGAS-STING signalling pathways. (monash.edu)
CGMP9
- Guanylate cyclase (GC) catalyzes the biosynthesis of cyclic guanosine 3',5'- monophosphate (cGMP) from GTP. (nih.gov)
- The mutated form synthesizes cyclic adenosine 3',5'-monophosphate instead of cGMP, allowing the detection of enzymatic activity by a reporter gene approach. (nih.gov)
- Nitric oxide (NO) and cyclic GMP (cGMP) suppressed glutamatergic synaptic transmission to trigeminal motoneurons in brain stem slices of neonatal rats. (nih.gov)
- One important second messenger in transducing the regulable nature of motile cilia is cyclic guanosine 3',5'-monophosphate (cGMP). (cdc.gov)
- Our findings are consistent with a functionally significant role of cAMP/PKA signaling (via cGMP inhibition of PDE3) and SR Ca(2+)in mediating the positive chronotropic effect of NO donors. (ox.ac.uk)
- During this process, second messengers such as cyclic nucleotides, cAMP and cGMP, are produced which serve to amplify the signal. (iisc.ac.in)
- The GC-C mediated cGMP signal transduction pathway also maintains intestinal crypt-villus axis homeostatis by exerting a cytostatic effect on the epithelial cells, there by regulating their turn over. (iisc.ac.in)
- Increasing evidence has suggested the possibility that the activation of N-methyl-D-aspartate (NMDA) receptors modulates spinal nociceptive transmission via a nitric oxide (NO)/cyclic guanosine 3',5'-monophosphate (cGMP) pathway. (silverchair.com)
- 2,3 NO increases cyclic guanosine 3′,5′-monophosphate (cGMP) through the activation of soluble guanylate cyclase (sGC). (silverchair.com)
Pathway4
- Scientists at University of Miami Miller School of Medicine's Sylvester Comprehensive Cancer Center say they have discovered how the stimulator of interferon genes (STING) signaling pathway may play an important role in alerting the immune system to cellular transformation. (pharmaceuticalintelligence.com)
- This is the first detailed examination of how the stimulator of interferon genes (STING) signaling pathway, discovered by Glen N. Barber, Ph.D., Leader of the Viral Oncology Program at Sylvester Comprehensive Cancer Center, may play an important role in alerting the immune system to cellular transformation. (pharmaceuticalintelligence.com)
- 14,15 Conversely, its pro-oxidant activity may enhance cellular defence against oxidants by stimulating the redox-regulated signal transduction pathway which leads to the gene expression of anti-oxidative enzymes such as heme oxygenase-1 (HO-1) and glutathione peroxidase (GPx). (rsc.org)
- However, in recent decades, several therapeutic strategies targeting the FGFR3 signaling pathway have been investigated. (e-apem.org)
Synthase14
- The biological role of cyclic di-GMP was first uncovered when it was identified as an allosteric activator of a cellulose synthase found in Gluconacetobacter xylinus in order to produce microbial cellulose. (wikipedia.org)
- In Gluconacetobacter xylinus, c-di-GMP stimulates the polymerization of glucose into cellulose as a high affinity allosteric activator of the enzyme cellulose synthase. (wikipedia.org)
- The Gluconacetobacter xylinus cellulose synthase is allosterically stimulated by cyclic di-GMP, presenting a mechanism by which cyclic di-GMP can regulate cellulose synthase activity. (wikipedia.org)
- This leads to the strong inference that conformational changes in PilZ domains allow the activity of targeted effector proteins (such as cellulose synthase) to be regulated by cyclic di-GMP. (wikipedia.org)
- His work in the fields of TLR7, Chemokine and Innate lymphoid cell overlaps with other areas such as Cyclic GMP-AMP synthase. (research.com)
- Cyclic GMP-AMP synthase (cGAS) senses foreign DNA to produce 2'3′-cyclic GMP-AMP (2'3′-cGAMP). (knoblauchpublishing.com)
- Cyclic GMP-AMP synthase (cGAS) is a cytosolic DNA sensor that activates a type-I interferon response. (medchemexpress.com)
- RU.521 (RU320521) is a potent and selective cyclic GMP-AMP synthase (cGAS) inhibitor and inhibits cGAS-mediated interferon upregulation. (medchemexpress.com)
- G150 is a highly selective human cyclic GMP-AMP synthase (h-cGAS) inhibitor with an IC 50 of 10.2 nM. (medchemexpress.com)
- G140 is a potent and selective inhibitor of cyclic GMP-AMP synthase (cGAS) , with IC 50 s of 14.0 nM and 442 nM for h-cGAS and m-cGAS, respectively. (medchemexpress.com)
- PF-06928215 is a cGAS (cyclic GMP-AMP Synthase) inhibitor with an IC 50 of 4.9 μΜ. (medchemexpress.com)
- IRAK4-IN-4 also inhibits cyclic GMP-AMP synthase ( cGAS ) with an IC 50 of 2.1 nM. (medchemexpress.com)
- cGAS-IN-1 (compound C20) is a flavonoid and Cyclic GMP-AMP Synthase (cGAS) inhibitor with IC 50 s of 2.28 μM (human cGAS) and 1.44 μM (mouse cGAS). (medchemexpress.com)
- The major sensor of cytosolic double stranded (ds)DNA is the enzyme cGAS (cyclic GMP-AMP synthase). (monash.edu)
Nucleotides1
- Nitric oxide (NO) donors increase heart rate (HR) through a guanylyl cyclase-dependent stimulation of the pacemaker current I(f), without affecting basal I(Ca-L). The activity of I(f)is known to be enhanced by cyclic nucleotides and by an increase in cytosolic Ca(2+). (ox.ac.uk)
Intracellular9
- Thus, a low concentration of signal in the environment, even as little as a single molecule, can yield a large intracellular signal and response. (axonmedchem.com)
- Parasites loaded with intracellular Ca 2+ chelators displayed significantly decreased infectivity and cyclic GMP level. (ias.ac.in)
- PGE1 increased intracellular levels of total inositol phosphates (IP), cyclic GMP, cyclic AMP, and calcium ([Ca2+]i). (shengsci.com)
- These data suggest that there may be subtypes of the PGE1 receptor in this clone: a high-affinity receptor mediating cyclic AMP formation, and a low-affinity receptor mediating IP accumulation, cyclic GMP formation, and intracellular calcium mobilization. (shengsci.com)
- Nitrate represses production of an important biofilm component, curli, and activates flagella via the modulation of intracellular cyclic-di-GMP levels. (knoblauchpublishing.com)
- Despite an improved understanding of how c-di-GMP signaling regulates S. Typhimurium biofilms, the processes that affect the intracellular c-di-GMP levels and the formation of multicellular communities in vivo during infections remain unknown. (knoblauchpublishing.com)
- Finally, we propose that PggH could modulate the activities of PDE-As and the intracellular concentration of c-di-GMP, resulting in phenotypic changes including in biofilm formation. (knoblauchpublishing.com)
- Hormones mobilize intracellular second messengers and initiate signalling cascades involving protein kinases and phosphatases, which are often spatially compartmentalized by anchoring proteins to increase signalling specificity 1 . (nature.com)
- Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. (bvsalud.org)
Protein6
- A protein kinase C activator, 4 beta-phorbol 12 beta-myristate 13 alpha-acetate, had opposite effects on PGE1-mediated IP release and cyclic GMP formation (inhibitory) and cyclic AMP formation (stimulatory). (shengsci.com)
- Pharmacological Inhibition of Protein Kinase G1 Enhances Bone Formation by Human Skeletal Stem Cells Through Activation of RhoA-Akt Signaling. (sdu.dk)
- HA-1004 is also a dual inhibitor of cyclic GMP-dependent protein kinase and cyclic AMP-dependent protein, and is involved in smooth muscle, second messenger, cyclic AMP and cyclic GMP regulation mechanisms. (medchemexpress.com)
- In this work, we have revealed that early viral protein UBCv1, the only known conjugating enzyme encoded by a virus, modulates innate immune and inflammatory signaling. (mdpi.com)
- This occurs through the downregulation of methylmalonyl coenzyme A epimerase (MCEE), mediated by an extracellular signal-regulated kinase 2-driven transcription factor Sp1/early growth response protein 1 transcriptional switch driven by metastatic signalling at its promoter level. (biomed.news)
- Activator of protein kinase A (cyclic AMP agonist). (biolog.de)
CGAS4
- cGAS can induce signaling that is known to promote the up-regulation of inflammatory genes and play a critical role in age-related macular degeneration and cellular senescence. (medchemexpress.com)
- In contrast, activation of IRF3 and ISRE signaling upon stimulation with TRIFΔRIP, cGAS/STING or RIG-I-CARD remained unaltered. (mdpi.com)
- Upon binding of dsDNA, cGAS produces a cyclic di-nucleotide molecule, cGAMP. (monash.edu)
- Our findings shed new light on the molecular mechanisms of cGAS-STING signalling and have important implications for the effective therapeutic targeting of STING-related diseases. (monash.edu)
Guanosine1
- synthesized by GGDEF domain-containing diguanylate cyclases and degraded by HD-GYP domain-containing phosphodiesterases (PDEs) to 2 GMP or by EAL domain-containing PDE-As to 5′-phosphoguanylyl-(3′,5′)-guanosine (pGpG). (knoblauchpublishing.com)
Nucleotide4
- We tested the hypothesis that beta-adrenergic hyperresponsiveness in the sinoatrial node (SAN) of the spontaneously hypertensive rat occurs at the level of the L-type calcium current because of altered cyclic nucleotide-dependent signaling. (ox.ac.uk)
- Decreased calcium current after cardiac nNOS gene transfer contributes to the normalization of beta-adrenergic hyperresponsiveness in the SAN from hypertensive rats by modulating cyclic nucleotide signaling. (ox.ac.uk)
- It was claimed to have a secondary function as a cyclic nucleotide-gated ion channel. (mdc-berlin.de)
- Considerably higher resistance against cyclic nucleotide phosphodiesterases compared to dibutyryl- or 8-Br-cAMP (Cat. (biolog.de)
Guanylate cyclase activity1
- Field M, Graf LH Jr, Laird WJ, Smith PL (1978) Heat-stable enterotoxin of Escherichia coli: In vitro effects on guanylate cyclase activity, cyclic GMP concentration, and ion transport in small intestine. (springer.com)
Motility3
- Processes that are known to be regulated by cyclic di-GMP, at least in some organisms, include biofilm formation (such as EPS matrices found by Steiner et al 2013), motility (especially the motile-to-sessile transition, see the review by Jenal et al 2017) and virulence factor production. (wikipedia.org)
- Cyclic GMP and cilia motility. (cdc.gov)
- In many bacteria, high levels of the ubiquitous second messenger c-di-GMP have been demonstrated to suppress motility and to promote the establishment of surface-adherent biofilm communities. (helmholtz-hzi.de)
Proteins6
- Cyclic di-GMP is synthesized by proteins with diguanylate cyclase activity. (wikipedia.org)
- Degradation of cyclic di-GMP is affected by proteins with phosphodiesterase activity. (wikipedia.org)
- Many proteins with GGDEF, EAL or HD-GYP domains are found with other domains that can receive signals, such as PAS domains. (wikipedia.org)
- A chemical proteomics approach to identify c-di-GMP binding proteins in Pseudomonas aeruginosa. (helmholtz-hzi.de)
- In this study, we have established a chemical proteomics approach to identify c-di-GMP interacting proteins in the opportunistic pathogen Pseudomonas aeruginosa. (helmholtz-hzi.de)
- A novel capture compound for the identification and analysis of cyclic di-GMP binding proteins. (helmholtz-hzi.de)
Degradation1
- While molecular mechanisms underlying the synthesis and degradation of c-di-GMP have been comprehensively characterized, little is known about how c-di-GMP mediates its regulatory effects. (helmholtz-hzi.de)
Calcium1
- PGE1-mediated IP accumulation, cyclic GMP formation, and [Ca2+]i increase depended on both the concentration of PGE1 and extracellular calcium ions. (shengsci.com)
Receptor3
- His primary areas of investigation include Cell biology, Immunology, Toll-like receptor, Signal transduction and Receptor. (research.com)
- Ho YJ, Burden LM, Hurley JH: "Structure of the GAF domain, a ubiquitous signaling motif and a new class of cyclic GMP receptor. (wheaton.edu)
- Disruption of PKA scaffolding mimics the interference of insulin with β-adrenergic receptor signalling. (nature.com)
Second messengers1
- Interestingly, signal transduction may be amplified significantly in the generation of second messengers, since initial stimulation may lead to the generation of many second messengers within the cell. (axonmedchem.com)
Diguanylate2
- Cyclic di-GMP (also called cyclic diguanylate and c-di-GMP) is a second messenger used in signal transduction in a wide variety of bacteria. (wikipedia.org)
- Some diguanylate cyclase enzymes are allosterically inhibited by cyclic di-GMP. (wikipedia.org)
Regulation2
- The PilZ domain has been shown to bind cyclic di-GMP and is believed to be involved in cyclic di-GMP-dependent regulation, but the mechanism by which it does this is unknown. (wikipedia.org)
- IMPORTANCE Recent studies provided important insight into our understanding of the role of c-di-GMP signaling and the regulation of enteric biofilms. (knoblauchpublishing.com)
Pseudomonas1
- For a review of c-di-GMP roles in Caulobacter crescentus, Pseudomonas aeruginosa, Komagataeibacter xylinus/Gluconacetobacter xylinus, Myxococcus xanthus, Bdellovibrio bacteriovorus and Pseudomonas fluorescens see Jenal et al 2017. (wikipedia.org)
Innate2
- In 2008, Glen N. Barber, Ph.D., leader of the viral oncology program at Sylvester, and professor and chairman of cell biology at the Miller School of Medicine, and colleagues published in Nature ("STING is an endoplasmic reticulum adaptor that facilitates innate immune signalling") the discovery of STING as a new cellular molecule that recognizes virus and bacteria infection to initiate host defense and immune responses. (pharmaceuticalintelligence.com)
- Dr Dominic De Nardo is leader of the Innate Immune Signalling Group in the Department of Biochemistry & Molecular Biology within the Monash Biomedicine Discovery Institute . (monash.edu)
Synthesis1
- Catalyzes the synthesis of cyclic-di-GMP (c-di-GMP) via the condensation of 2 GTP molecules. (string-db.org)
Immune3
- Adjuvants formulated with a TLR9 agonist, CpG-2722, with various cyclic dinucleotides (CDNs) that are STING agonists increased germinal center B cell response and elicited humoral immune responses in immunized mice. (ijbs.com)
- Here, we review the status of 2'3′-cGAMP research and outline the role of 2'3′-cGAMP in immune signaling, adjuvant applications, and cancer immunotherapy, as well as various 2'3′-cGAMP detection methods. (knoblauchpublishing.com)
- In this study we show, for the first time, that STING signaling is repressed in colorectal carcinoma and other cancers, an event which may enable transformed cells to evade the immune system. (pharmaceuticalintelligence.com)
Cascades1
- Signal-transduction cascades mediate the sensing and processing of these stimuli. (axonmedchem.com)
Mechanisms3
- Cyclic di-GMP levels are regulated using a variety of mechanisms. (wikipedia.org)
- Cyclic di-GMP levels regulate other processes via a number of mechanisms. (wikipedia.org)
- Currently, the molecular mechanisms involved in induction of oocyte meiotic resumption in the pre-ovulatory follicle which may include (involve) the elimination of meiosis inhibiting factors and/or the accumulation or activation of oocyte matu-ration signals are actively studied. (kiev.ua)
STING6
- In the new study, published in Cell Reports ("Deregulation of STING Signaling in Colorectal Carcinoma Constrains DNA Damage Responses and Correlates With Tumorigenesis"), they describe STING's role in the potential suppression of colorectal cancer. (pharmaceuticalintelligence.com)
- Using disease models of colorectal cancer, the team of Sylvester scientists showed that loss of STING signaling negatively affected the body's ability to recognize DNA-damaged cells. (pharmaceuticalintelligence.com)
- He and his colleagues suggest evaluating STING signaling as a prognostic marker for the treatment of colorectal as well as other cancers. (pharmaceuticalintelligence.com)
- For example, Dr. Barber's study showed that cancer cells with defective STING signaling were particularly prone to attack by oncolytic viruses presently being used as cancer therapies. (pharmaceuticalintelligence.com)
- Trafficking of STING to the Golgi leads to clustering of STING, providing a platform for the initiation of signal transduction. (monash.edu)
- Post-Golgi, STING is located in endosome and later lysosomal vesicles, which appears important for termination of signalling. (monash.edu)
Eukaryotes3
- Cyclic di-GMP is not known to be used by archaea, and has only been observed in eukaryotes in Dictyostelium. (wikipedia.org)
- As part of nitric oxide-cyclic GMP transduction signaling operative in higher eukaryotes and involved in the long-term potentiation, a soluble guanylyl cyclase has also been detected in this lower eukaryote. (ias.ac.in)
- Cyclic GMP is emerging as a universal second messenger, and is found in both prokaryotes and eukaryotes. (iisc.ac.in)
Accumulation3
- There was more than a 10-fold difference between the ED50 for PGE1 at cyclic AMP formation (70 nM) and its ED50 values at IP accumulation (1 microM), cyclic GMP formation (2 microM), and [Ca2+]i increase (5 microM). (shengsci.com)
- PGE1 had more potent intrinsic activity in cyclic AMP formation, IP accumulation, and cyclic GMP formation than did PGE2, PGF2 alpha, or PGD2. (shengsci.com)
- Since excess pGpG feedback inhibits PDE-A activity and thereby can lead to the uncontrolled accumulation of c-di-GMP, a PDE that degrades pGpG to 2 GMP (PDE-B) has been presumed to exist. (knoblauchpublishing.com)
Amplify1
- These molecular circuits detect, amplify, and integrate diverse external signals to generate responses such as changes in enzyme activity, gene expression, phenotypic alterations, or ion-channel activity. (axonmedchem.com)
Receptors3
- In its absence, several light-oxygen-voltage receptors invariably retained productive, if often attenuated, signaling responses. (nature.com)
- Signaling without glutamine appears intrinsic to light-oxygen-voltage receptors, which pertains to biotechnological applications and suggests evolutionary descendance from redox-active flavoproteins. (nature.com)
- Upon an environmental signal, Membrane receptors transfer information from the environment to the cell's interior. (axonmedchem.com)
Enzymes1
- Enzymes that degrade or synthesize cyclic di-GMP are believed to be localized to specific regions of the cell, where they influence receivers in a restricted space. (wikipedia.org)
Inflammatory1
- this indicates that there is a close molecular and signaling link between inflammatory response and autophagy. (medchemexpress.com)
Overexpression1
- swimming returnes to normal when residues 206-207 are both mutated to Ala. Overexpression also leads to a reduction in flagellar abundance and a 20-fold increase in c-di-GMP levels in vivo. (string-db.org)
Gene expression1
- Riboswitches called the cyclic di-GMP-I riboswitch and cyclic di-GMP-II riboswitch regulate gene expression in response to cyclic di-GMP concentrations in a variety of bacteria, but not all bacteria that are known to use cyclic di-GMP. (wikipedia.org)
Increases1
- Contact with surfaces increases c-di-GMP which increases transcription, translation, and post translation of exopolysaccharides (EPSs) and other extracellular polymeric substance matrix components (see the review by Jenal et al 2017). (wikipedia.org)
Vitro1
- 2'-AHC-c-di-GMP was also employed in surface plasmon resonance studies to evaluate and quantify the interaction of c-di-GMP with its potential target molecules in vitro. (helmholtz-hzi.de)
Contrast1
- In contrast, pretreatment with Ca 2+ ionophores, which elevated Ca 2+ levels in L. donovani, significantly enhanced the cyclic GMP level as well as the infectivity of the parasites. (ias.ac.in)
Cells1
- Prostaglandin E1 (PGE1)-mediated transmembrane signal control systems were investigated in intact murine neuroblastoma cells (clone N1E-115). (shengsci.com)
TRIF1
- Satoshi Uematsu has included themes like TRIF and Myeloid Differentiation Factor 88 in his Signal transduction study. (research.com)
Transient1
- As recently proposed 25 , glutamine reorientation, and signal propagation may be aided by transient rearrangements of two conserved asparagine residues that coordinate the pteridin portion of the flavin. (nature.com)