Nucleotides targets effector cyclic gmp dependent protein kinases. Medical search. Frequent questions

As can be seen in the cyclic adenosine monophosphate (cAMP) and cyclic guanosine monophosphate (cGMP) images, the 'cyclic' portion consists of two bonds between the phosphate group and the 3' and 5' hydroxyl groups of the sugar, very often a ribose. (wikipedia.org)
Evgeny Fesenko, Stanislav Kolesnikov, and Arkady Lyubarsky discovered in 1985 that cyclic guanosine monophosphate (cGMP) can initiate the photoresponse in rods. (wikipedia.org)
cAMP is 3'5'-cyclic adenosine monophosphate, cGMP is 3'5'-cyclic guanosine monophosphate, cCMP is cytidine 3',5'-monophosphate, and cUMP is uridine 3',5'-cyclic phosphate. (wikipedia.org)
Cyclic GMP-dependent protein kinases (PKGs) are key mediators of the nitric oxide/cyclic guanosine monophosphate (cGMP) signaling pathway that regulates biological functions as diverse as smooth muscle contraction, cardiac function, and axon guidance. (bvsalud.org)

Understanding how cGMP differentially triggers mammalian PKG isoforms could lead to new therapeutics that inhibit or activate PKGs, complementing drugs that target nitric oxide synthases and cyclic nucleotide phosphodiesterases in this signaling axis. (bvsalud.org)
Sperm intracellular cAMP levels depend on the activity of adenylyl cyclases, mostly SACY, though transmembrane-containing adenylyl cyclases are also present, and on the activity of cyclic nucleotide phosphodiesterases (PDE) whose role is to degrade cAMP into 5'-AMP. (plos.org)
Enzymerhodopsins represent a recently discovered class of rhodopsins which includes histidine kinase rhodopsin, rhodopsin phosphodiesterases, and rhodopsin guanylyl cyclases (RGCs). (elifesciences.org)

Protein kinase G type Iα (PKGIα) and adenosine monophosphate-dependent kinase (AMPK) affect the contractile apparatus of podocytes and influence the permeability of the GFB. (bvsalud.org)
In mammals, adenosine 3', 5'-cyclic monophosphate (cAMP) is known to play highly important roles in sperm motility and acrosomal exocytosis. (plos.org)
Cyclic AMP (adenosine 3', 5'-cyclic monophosphate) is an important player in sperm function. (plos.org)
The two well-established cyclic nucleotides are adenosine-3',5'-cyclic monophosphate (cyclic AMP) and guanine-3',5'-cyclic monophosphate (cyclic GMP). (pancreapedia.org)

Wei-Jen Tang and James Hurley reported in 1998 that adenylyl cyclase, which synthesizes cAMP, is regulated not only by hormones and neurotransmitters, but also by phosphorylation, calcium, forskolin, and guanine nucleotide-binding proteins (G proteins). (wikipedia.org)
It is known to act through protein phosphorylation via PRKA and through the activation of guanine nucleotide exchange factors like EPAC. (plos.org)
After a ligand binds to the GPCR, it activates a heterotrimeric G-protein, which is composed of three subunits: a guanine nucleotide binding α-subunit, and a βγ-heterodimer (98). (pancreapedia.org)

Like other nucleotides, cyclic nucleotides are composed of three functional groups: a sugar, a nitrogenous base, and a single phosphate group. (wikipedia.org)
While all nucleotides have this structure, the phosphate group makes a second connection to the ribose ring at the 3' carbon in cyclic nucleotides. (wikipedia.org)
Because the phosphate group has two separate bonds to the ribose sugar, it forms a cyclic ring. (wikipedia.org)
A cyclic nucleotide, unlike other nucleotides, has a cyclic bond arrangement between the ribose sugar and the phosphate group. (pancreapedia.org)
Cyclic nucleotides form when the phosphate group of the molecule of nucleotide triphosphate (ATP or GTP) is attacked by the 3' hydroxyl group of the ribose, forming a cyclic 3',5'-phosphate ester with release of pyrophosphate. (pancreapedia.org)

Upon binding of dsDNA, cGAS produces a cyclic di-nucleotide molecule, cGAMP. (monash.edu)

These results suggest that NO contributes to L-LTP by stimulating guanylyl cyclase and cGMP-dependent protein kinase, which acts in parallel with PKA to increase phosphorylation of the transcription factor CREB. (jneurosci.org)
Previously, IRAG1 was discovered as a 125 kDa membrane protein at the endoplasmic reticulum, which is associated with the intracellular Ca2+ channel IP3R-I and the PKGIß and inhibits IP3R-I upon PKGIß-mediated phosphorylation. (bvsalud.org)
AMPKα2 siRNA increased basal levels of phosphorylated myosin phosphate target subunit 1 and decreased the phosphorylation of myosin light chain 2. (bvsalud.org)
PHOSPHORYLATION of IRF-3 causes the protein to be translocated from the CYTOPLASM to CELL NUCLEUS where it binds DNA , and activates transcription. (lookformedical.com)

Three-train L-LTP was also blocked by inhibitors of guanylyl cyclase or cGMP-dependent protein kinase (PKG). (jneurosci.org)
In these photoreceptors, the C-terminus of the rhodopsin is directly linked to either a histidine kinase (histidine kinase rhodopsin), a phosphodiesterase (rhodopsin phosphodiesterase, RPDE), or a guanylyl cyclase (rhodopsin guanylyl cyclase, RGC). (elifesciences.org)

Non-antibody proteins secreted by inflammatory leukocytes and some non-leukocytic cells, that act as intercellular mediators. (lookformedical.com)

One mechanism is the binding of an extracellular ligand to a transmembrane G-protein-coupled receptor (GPCR). (pancreapedia.org)
The receptor protein has seven transmembrane α-helices connected by alternating cytosolic and extracellular loops. (pancreapedia.org)
The ligand-binding site is in the extracellular domain and the cytosolic domain has a heterotrimeric G protein-binding site (127). (pancreapedia.org)
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)
Recently, a large number of signaling proteins reported play an important key role in the process of LPLI-induced cell proliferation, probably due to the fact that the molecular events they are involved in are the basic response of the cells to extracellular stimuli. (biomedcentral.com)

cGMP-dependent protein kinase I-α (PKG1α) is a target for pulmonary arterial hypertension due to its role in the regulation of smooth muscle function. (bvsalud.org)
The Plasmodium falciparum cGMP-dependent protein kinase (PfPKG) is one of the key regulators of the malaria parasite life cycle in both sexual and asexual blood-stages. (biomedcentral.com)
In addition, disrupting cGMP binding through mutating the conserved arginine 492 to lysine (R492K) abolished the cGMP-dependent activation of the deletion mutant (500-600 fold higher K A for cGMP), suggesting that the cGMP binding at the CNB-D mainly triggers the activation of this mutant. (biomedcentral.com)
Kim JJ, Flueck C, Franz E, Sanabria-Figueroa E, Thompson E, Lorenz R, et al: Crystal structures of the carboxyl cGMP binding domain of the Plasmodium falciparum cGMP-dependent protein kinase reveal a novel capping triad crucial for merozoite egress. (biomedcentral.com)

Our results indicate that context-dependent recruitment of alternative intracellular signaling pathways within a single sensory neuron type conveys opposite hedonic valences, thereby providing a robust mechanism for odorant encoding and discrimination at the periphery. (plos.org)
In addition to antiviral activity, it activates NATURAL KILLER CELLS and B-LYMPHOCYTES , and down-regulates VASCULAR ENDOTHELIAL GROWTH FACTOR expression through PI-3 KINASE and MAPK KINASES signaling pathways. (lookformedical.com)
This new generation may rival the so-called magic bullets in the treatment of diseases that arise as a consequence of the deregulation of multiple signaling pathways provided the challenge of optimization of the activities shown by the pharmacophores with the different targets is addressed. (biomedcentral.com)

Goupil S, Maréchal L, El Hajj H, Tremblay M-È, Richard FJ, Leclerc P (2016) Identification and Localization of the Cyclic Nucleotide Phosphodiesterase 10A in Bovine Testis and Mature Spermatozoa. (plos.org)

Fig. 1: Photochemistry of light-oxygen-voltage receptors and sequences of proteins under study. (nature.com)
As a sub-objective, since PDE10A transcript variants were reported strictly through analyses of bovine genomic sequence, we also wanted to determine the nucleotide and amino acid sequences by experimental evidence. (plos.org)
IRF proteins bind specific DNA sequences such as interferon-stimulated response elements, interferon regulatory elements, and the interferon consensus sequence. (lookformedical.com)
Descriptions of specific amino acid, carbohydrate, or nucleotide sequences which have appeared in the published literature and/or are deposited in and maintained by databanks such as GENBANK, European Molecular Biology Laboratory (EMBL), National Biomedical Research Foundation (NBRF), or other sequence repositories. (lookformedical.com)
The essential steps include thermal denaturation of the double-stranded target molecules, annealing of the primers to their complementary sequences, and extension of the annealed primers by enzymatic synthesis with DNA polymerase. (lookformedical.com)

Hepatocyte growth factor receptor (c-Met), a member of tyrosine protein kinase receptors (TPKR), is phosphorylated during LPLI-induced proliferation, but tumor necrosis factor alpha (TNF-alpha) receptor has not been affected. (biomedcentral.com)

The understanding of the concept of second messengers, and in particular the role of cyclic nucleotides and their ability to relay physiological signals to a cell, has its origins in the research of glycogen metabolism by Carl and Gerty Cori, for which they were awarded a Nobel Prize in Physiology or Medicine in 1947. (wikipedia.org)
Both cyclic AMP and cyclic GMP are second messengers. (pancreapedia.org)

We discovered that IKKe works redundantly along with TBK1, the major effector kinase downstream of STING. (monash.edu)
To test a possible downstream target of PKG, we examined changes in phospho-CRE-binding protein (phospho-CREB) immunofluorescence in the CA1 cell body area and obtained results similar to those of the electrophysiology experiments. (jneurosci.org)
in an operon with an upstream PurR/LacI-type transcriptional regulator gene, named amlR ( ACSP50_2475 ), and a gene downstream ( ACSP50_2473 ) encoding a GGDEF-EAL-domain-containing protein putatively involved in c-di-GMP signaling. (frontiersin.org)
We ascribe these effects to ACSP50_2473 , which is localized downstream of amlE and presumably involved in the metabolism of the second messenger c-di-GMP. (frontiersin.org)

The lcn2-induced phenotypic changes of astrocytes occurred through a Rho-ROCK (Rho kinase)-GFAP pathway, which was positively regulated by nitric oxide and cGMP. (jneurosci.org)
Moreover, PKGIα siRNA activated the AMPK-dependent signaling pathway. (bvsalud.org)
The described setup and experimental design enable real-time monitoring of substrate turnover in light-activated enzymes on a molecular scale, thus opening the pathway to a deeper understanding of enzyme activity and protein-protein interactions. (elifesciences.org)

They have been identified as secondary messengers in both hormone and ion-channel signalling in eukaryotic cells, as well as allosteric effector compounds of DNA binding proteins in prokaryotic cells. (wikipedia.org)
Selected molecules were crystallized in the presence of PKG1α and were found to bind to an allosteric site proximal to the low-affinity nucleotide binding domain. (bvsalud.org)
However, it could be activated efficiently by cGMP (7.0 U/mg), suggesting that the allosteric activation mechanism of PfPKG is dependent only on cGMP binding. (biomedcentral.com)

The role of cyclic uridine monophosphate (cUMP) is even less well known. (wikipedia.org)
The non-canonical cyclic nucleotides include the purines inosine-3',5'-cyclic monophosphate (cyclic IMP), xanthosine-3',5'-cyclic monophosphate (cyclic XMP) and the pyrimidines cytidine-3',5'-cyclic monophosphate (cyclic cCMP), uridine-3',5'-cyclic monophosphate (cyclic UMP), and thymidine-3',5'-cyclic monophosphate (cTMP) (145). (pancreapedia.org)

Here, we demonstrate that HlgCB, another leucocidin, which targets the same receptors as PVL, highly contributes to S. aureus virulence in -negative strains. (cnrs.fr)

cAMP and cGMP are currently the most well documented cyclic nucleotides, however there is evidence that cCMP (with cytosine) is also involved in eukaryotic cellular messaging. (wikipedia.org)
The two most well-studied cyclic nucleotides are cyclic AMP (cAMP) and cyclic GMP (cGMP), while cyclic CMP (cCMP) and cyclic UMP (cUMP) are less understood. (wikipedia.org)

The major sensor of cytosolic double stranded (ds)DNA is the enzyme cGAS (cyclic GMP-AMP synthase). (monash.edu)
A cyclase enzyme (lyase) catalyzes the formation of the cyclic nucleotide from its nucleotide triphosphate precursor ( Figure 1 ). (pancreapedia.org)

A cyclic nucleotide (cNMP) is a single-phosphate nucleotide with a cyclic bond arrangement between the sugar and phosphate groups. (wikipedia.org)

Conversely, either NO or cGMP analogs paired with one-train tetanization produced late-phase potentiation, and the cGMP-induced potentiation was blocked by inhibitors of protein or RNA synthesis and an inhibitor of PKG, but not by an inhibitor of PKA. (jneurosci.org)

In this study, we investigated the adjuvant activities of combinations of Toll-like receptor 9 (TLR9) and stimulator of interferon genes (STING) agonists in a SARS-CoV-2 receptor binding domain protein vaccine. (ijbs.com)

This cyclic conformation allows cyclic nucleotides to bind to proteins to which other nucleotides cannot. (pancreapedia.org)
Alpha-crystallins also act as molecular chaperones that bind to denatured proteins, keep them in solution and thereby maintain the translucency of the lens. (lookformedical.com)

Here, we review mechanisms of mitochondrial gene expression with a focus on the recent findings in the field of mammalian mtDNA transcription and disease phenotypes caused by defects in proteins involved in this process. (biomed.news)
This work illustrates the subtlety of regulatory mechanisms in bacteria, especially the sometimes major effects on phenotypes of single nucleotide variation in noncoding regions. (cnrs.fr)

3 hr, and is reduced by inhibitors of PKA and of protein or RNA synthesis. (jneurosci.org)

Discovery of cyclic nucleotides has contributed greatly to the understanding of kinase and phosphatase mechanisms, as well as protein regulation in general. (wikipedia.org)
Cyclic nucleotide signaling can be initiated by two general mechanisms. (pancreapedia.org)
The mechanisms underlying context-dependent flexibility in odor valence are not fully understood. (plos.org)
We review the state of the art with such combinations that have an epigenetic target as one of their mechanisms of action. (biomedcentral.com)

In 1992 Lawrence Haynes and King-Wai Yau uncovered cNMP's role in the light-dependent cyclic-nucleotide-gated channel of cone photoreceptors. (wikipedia.org)

Microbial rhodopsins (Rhs) are transmembrane proteins that utilize light-induced isomerization of their retinal cofactor to function as light-sensitive ion channels, pumps and sensors. (elifesciences.org)

The interferon alpha-beta receptor signals through the action of JANUS KINASES such as the TYK2 KINASE. (lookformedical.com)
Staphylococcus aureus gamma-hemolysin CB (HlgCB) is a core-genome-encoded pore-forming toxin that targets the C5a receptor, similar to the phage-encoded Panton-Valentine leucocidin (PVL). (cnrs.fr)

The end products of this catalytic reaction are a cyclic nucleotide (cyclic AMP or cyclic GMP) and a pyrophosphate group. (pancreapedia.org)
Without the auto-inhibitory sequence, we expected that the mutant would completely lose its control on the activity, since the catalytic cleft of the kinase is open. (biomedcentral.com)
Upon cGMP binding, conformational changes in the regulatory (R) domain, especially in the area that bridges the regulatory and catalytic domains, induce kinase activation. (biomedcentral.com)

At steady state, STING is an endoplasmic reticulum (ER) resident protein that exists as a preformed dimer. (monash.edu)

Although more than 50 years have passed since their initial discovery, interest in cyclic nucleotides and their biochemical and physiological significance continues. (wikipedia.org)
This review aims to highlight the recent research regarding these two regulatory proteins to envision their molecular and (patho-)physiological tasks and to unravel their functional interplay as possible (patho-)physiological counterparts. (bvsalud.org)

Proteins secreted by vertebrate cells in response to a wide variety of inducers. (lookformedical.com)
A heterogeneous family of water-soluble structural proteins found in cells of the vertebrate lens. (lookformedical.com)

If its negative charge is not reduced, the nucleotide triphosphate cannot be approached by a nucleophile, which is, in this reaction, the 3' hydroxyl group of the ribose (183). (pancreapedia.org)

Understanding this newly identified molecular mechanism in podocytes provides further insights into the pathogenesis of glomerular disease and novel therapeutic targets for glomerulopathies. (bvsalud.org)
Efforts are underway to use chemoinformatics to help understand drug effects from a signal transduction network perspective [ 3 ], to confidently predict new molecular targets for known drugs, and to explain polypharmacology. (biomedcentral.com)
To decipher the molecular basis for the variation in expression and protein production among strains, different regulation levels were analyzed in representative clinical isolates and reference strains. (cnrs.fr)

Depending on which family the G protein is, it goes on to activate (G αs protein subunit) or inhibit (G αi protein subunit) the membrane-bound cyclase. (pancreapedia.org)
An interleukin-1 subtype that is synthesized as an inactive membrane-bound pro-protein. (lookformedical.com)

Stat1 interacts with P53 TUMOR SUPPRESSOR PROTEIN and regulates expression of GENES involved in growth control and APOPTOSIS . (lookformedical.com)

After the spectroscopic characterization of the late rhodopsin photoproducts, we analyzed truncated variants and revealed the involvement of the cytosolic N-terminus in the structural rearrangements upon photo-activation of the protein. (elifesciences.org)

Taylor HM, McRobert L, Grainger M, Sicard A, Dluzewski AR, Hopp CS, et al: The Malaria Parasite Cyclic GMP-Dependent Protein Kinase Plays a Central Role in Blood-Stage Schizogony. (biomedcentral.com)

LCN2 protein induced upregulation of glial fibrillary acidic protein (GFAP), cell migration, and morphological changes similar to characteristic phenotypic changes termed reactive astrocytosis. (jneurosci.org)
C-reactive protein (CRP) was often increased and very high CRPs were associated with a less favorable outcome for the patient. (spandidos-publications.com)

In cancer, the design and synthesis of new molecules that simultaneously modulate multiple biochemically distinct oncogenic targets is of current interest. (biomedcentral.com)

Efficient inactivated or protein vaccines typically rely on an effective adjuvant to elicit an immune response and boost vaccine activity. (ijbs.com)

To benefit from those effects, it is required that the multitarget drug exhibit balanced in vitro and in vivo activities to match potency for the corresponding targets, as well as optimized PK and safety profiles. (biomedcentral.com)

Altogether, we present a previously uncharacterized dysregulation of propionate metabolism as an important contributor to cancer and a valuable potential target in the therapeutic treatment of metastatic carcinomas. (biomed.news)
Another current trend in therapy is drug repurposing or the re-discovery of a new therapeutic area for a drug used traditionally to treat a given pathology, either through the ability to modulate an additional target or by the involvement of the primary target in multiple pathologies. (biomedcentral.com)

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)
CpG-2722 induced antigen-dependent T helper (Th)1 and Th17 responses, while 2'3'-c-di-AM(PS)2 induced a Th2 response. (ijbs.com)
The combination of CpG-2722 and 2'3'-c-di-AM(PS)2 generated a distinct antigen-dependent Th response profile characterized by higher Th1 and Th17, but lower Th2 responses. (ijbs.com)
Thus, the antigen-dependent Th responses observed in the animals immunized with different vaccines were shaped by the antigen-independent cytokine-inducing profiles of their adjuvant. (ijbs.com)

Their biological significance includes a broad range of protein-ligand interactions. (wikipedia.org)

LPLI-induced cell cycle progression can be regulated by the activation or elevated expressions of cell cycle-specific proteins. (biomedcentral.com)

Iron and BIM (Bcl-2-interacting mediator of cell death) proteins were involved in the cytotoxic sensitization process. (jneurosci.org)
Although a high level of PDE10A gene expression is observed in the testis, information on the identity of the isoforms or on the cell type that express the PDE10 protein is lacking. (plos.org)
This context-dependent reversal of odorant preference is driven by cell-autonomous inversion of the response to these alcohols in the single AWC olfactory neuron pair. (plos.org)
This approach was based on the assumption that the deregulation of a protein was causally linked to a disease state, and the pharmacological intervention through inhibition of the deregulated target was able to restore normal cell function. (biomedcentral.com)

There are two main groups of cyclic nucleotides: the canonical or well-established and the non-canonical or unknown-function cyclic nucleotides. (pancreapedia.org)

The modern drug discovery process has largely focused its attention in the so-called magic bullets, single chemical entities that exhibit high selectivity and potency for a particular target. (biomedcentral.com)
In addition, ligands are being discovered which, as single chemical entities, are able to modulate multiple epigenetic targets simultaneously (multitarget epigenetic drugs). (biomedcentral.com)
Notwithstanding the success of combination therapy, the use of a single drug that modulates several targets might be therapeutically advantageous over the use of drugs in combination. (biomedcentral.com)
Strikingly, only one single nucleotide polymorphism (SNP) in the 5' untranslated region (UTR) of mRNA strongly impaired translation in the USA300 strain, leading to a strong decrease in the level of HlgC but not in HlgB. (cnrs.fr)

Anatomy22

Organisms13

Chemicals and Drugs159

Analytical, Diagnostic and Therapeutic Techniques and Equipment11

Phenomena and Processes47

Information Science3

Guanosine monophosphate4

Phosphodiesterases3

Adenosine4

Guanine3

Phosphate group5

Molecule1

Phosphorylation4

Guanylyl cyclase2

Mediators1

Extracellular5

CGMP-dependent4

Pathways3

Phosphodiesterase1

Sequences5

Tyrosine1

Second messengers2

Downstream4

Pathway3

Allosteric3

Monophosphate2

Receptors1

CCMP2

Enzyme2

Bond arrangement1

Inhibitor1

Stimulator1

Bind2

Phenotypes2

Inhibitors1

Mechanisms4

Photoreceptors1

Transmembrane1

Receptor2

Catalytic3

Endoplasmic reticulum1

Physiological2

Vertebrate2

Reaction1

Molecular3

Membrane-bound2

Regulates1

Cytosolic1

Role1

Reactive2

Synthesis1

Elicit1

Vivo1

Therapeutic2

Responses4

Interactions1

Activation1

Cell4

Groups1

Single4