An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. The additional presence of DIACYLGLYCEROLS markedly increases its sensitivity to both calcium and phospholipids. The sensitivity of the enzyme can also be increased by PHORBOL ESTERS and it is believed that protein kinase C is the receptor protein of tumor-promoting phorbol esters.
A family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
A CALCIUM and CALMODULIN-dependent cyclic nucleotide phosphodiesterase subfamily. The three members of this family are referred to as type 1A, type 1B, and type 1C and are each product of a distinct gene. In addition, multiple enzyme variants of each subtype can be produced due to multiple alternative mRNA splicing. Although the type 1 enzymes are classified as 3',5'-cyclic-AMP phosphodiesterases (EC, some members of this class have additional specificity for CYCLIC GMP.
Guanosine cyclic 3',5'-(hydrogen phosphate). A guanine nucleotide containing one phosphate group which is esterified to the sugar moiety in both the 3'- and 5'-positions. It is a cellular regulatory agent and has been described as a second messenger. Its levels increase in response to a variety of hormones, including acetylcholine, insulin, and oxytocin and it has been found to activate specific protein kinases. (From Merck Index, 11th ed)
An adenine nucleotide containing one phosphate group which is esterified to both the 3'- and 5'-positions of the sugar moiety. It is a second messenger and a key intracellular regulator, functioning as a mediator of activity for a number of hormones, including epinephrine, glucagon, and ACTH.
A group of enzymes that are dependent on CYCLIC AMP and catalyze the phosphorylation of SERINE or THREONINE residues on proteins. Included under this category are two cyclic-AMP-dependent protein kinase subtypes, each of which is defined by its subunit composition.
Enzymes that catalyze the hydrolysis of CYCLIC AMP to form adenosine 5'-phosphate. The enzymes are widely distributed in animal tissue and control the level of intracellular cyclic AMP. Many specific enzymes classified under this heading demonstrate additional spcificity for 3',5'-cyclic IMP and CYCLIC GMP.
The monomeric units from which DNA or RNA polymers are constructed. They consist of a purine or pyrimidine base, a pentose sugar, and a phosphate group. (From King & Stansfield, A Dictionary of Genetics, 4th ed)
Nucleoside-2',3'-cyclic phosphate nucleotidohydrolase. Enzymes that catalyze the hydrolysis of the 2'- or 3'- phosphate bonds of 2',3'-cyclic nucleotides. Also hydrolyzes nucleoside monophosphates. Includes EC and EC EC 3.1.4.-.
A CALMODULIN-dependent enzyme that catalyzes the phosphorylation of proteins. This enzyme is also sometimes dependent on CALCIUM. A wide range of proteins can act as acceptor, including VIMENTIN; SYNAPSINS; GLYCOGEN SYNTHASE; MYOSIN LIGHT CHAINS; and the MICROTUBULE-ASSOCIATED PROTEINS. (From Enzyme Nomenclature, 1992, p277)
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
Agents that inhibit PROTEIN KINASES.
A superfamily of PROTEIN-SERINE-THREONINE KINASES that are activated by diverse stimuli via protein kinase cascades. They are the final components of the cascades, activated by phosphorylation by MITOGEN-ACTIVATED PROTEIN KINASE KINASES, which in turn are activated by mitogen-activated protein kinase kinase kinases (MAP KINASE KINASE KINASES).
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.
An intracellular signaling system involving the MAP kinase cascades (three-membered protein kinase cascades). Various upstream activators, which act in response to extracellular stimuli, trigger the cascades by activating the first member of a cascade, MAP KINASE KINASE KINASES; (MAPKKKs). Activated MAPKKKs phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES which in turn phosphorylate the MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs). The MAPKs then act on various downstream targets to affect gene expression. In mammals, there are several distinct MAP kinase pathways including the ERK (extracellular signal-regulated kinase) pathway, the SAPK/JNK (stress-activated protein kinase/c-jun kinase) pathway, and the p38 kinase pathway. There is some sharing of components among the pathways depending on which stimulus originates activation of the cascade.
A cyclic nucleotide phosphodiesterase subfamily that is inhibited by the binding of CYCLIC GMP to an allosteric domain found on the enzyme and through phosphorylation by regulatory kinases such as PROTEIN KINASE A and PROTEIN KINASE B. The two members of this family are referred to as type 3A, and type 3B, and are each product of a distinct gene. In addition multiple enzyme variants of each subtype can be produced due to multiple alternative mRNA splicing.
Conversion of an inactive form of an enzyme to one possessing metabolic activity. It includes 1, activation by ions (activators); 2, activation by cofactors (coenzymes); and 3, conversion of an enzyme precursor (proenzyme or zymogen) to an active enzyme.
A mitogen-activated protein kinase subfamily that regulates a variety of cellular processes including CELL GROWTH PROCESSES; CELL DIFFERENTIATION; APOPTOSIS; and cellular responses to INFLAMMATION. The P38 MAP kinases are regulated by CYTOKINE RECEPTORS and can be activated in response to bacterial pathogens.
Phosphotransferases that catalyzes the conversion of 1-phosphatidylinositol to 1-phosphatidylinositol 3-phosphate. Many members of this enzyme class are involved in RECEPTOR MEDIATED SIGNAL TRANSDUCTION and regulation of vesicular transport with the cell. Phosphatidylinositol 3-Kinases have been classified both according to their substrate specificity and their mode of action within the cell.
A class of enzymes that catalyze the hydrolysis of one of the two ester bonds in a phosphodiester compound. EC 3.1.4.
The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.
Compounds which inhibit or antagonize the biosynthesis or actions of phosphodiesterases.
A cyclic nucleotide phosphodiesterase subfamily that is activated by the binding of CYCLIC GMP to an allosteric domain found on the enzyme. Multiple enzyme variants of this subtype can be produced due to multiple alternative mRNA splicing. The subfamily is expressed in a broad variety of tissues and may play a role in mediating cross-talk between CYCLIC GMP and CYCLIC CMP pathways. Although the type 2 enzymes are classified as 3',5'-cyclic-AMP phosphodiesterases (EC, members of this class have additional specificity for CYCLIC GMP.
A proline-directed serine/threonine protein kinase which mediates signal transduction from the cell surface to the nucleus. Activation of the enzyme by phosphorylation leads to its translocation into the nucleus where it acts upon specific transcription factors. p40 MAPK and p41 MAPK are isoforms.
The intracellular transfer of information (biological activation/inhibition) through a signal pathway. In each signal transduction system, an activation/inhibition signal from a biologically active molecule (hormone, neurotransmitter) is mediated via the coupling of a receptor/enzyme to a second messenger system or to an ion channel. Signal transduction plays an important role in activating cellular functions, cell differentiation, and cell proliferation. Examples of signal transduction systems are the GAMMA-AMINOBUTYRIC ACID-postsynaptic receptor-calcium ion channel system, the receptor-mediated T-cell activation pathway, and the receptor-mediated activation of phospholipases. Those coupled to membrane depolarization or intracellular release of calcium include the receptor-mediated activation of cytotoxic functions in granulocytes and the synaptic potentiation of protein kinase activation. Some signal transduction pathways may be part of larger signal transduction pathways; for example, protein kinase activation is part of the platelet activation signal pathway.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
The rate dynamics in chemical or physical systems.
A cytoplasmic serine threonine kinase involved in regulating CELL DIFFERENTIATION and CELLULAR PROLIFERATION. Overexpression of this enzyme has been shown to promote PHOSPHORYLATION of BCL-2 PROTO-ONCOGENE PROTEINS and chemoresistance in human acute leukemia cells.
A serine-threonine protein kinase family whose members are components in protein kinase cascades activated by diverse stimuli. These MAPK kinases phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES and are themselves phosphorylated by MAP KINASE KINASE KINASES. JNK kinases (also known as SAPK kinases) are a subfamily.
A ubiquitously expressed protein kinase that is involved in a variety of cellular SIGNAL PATHWAYS. Its activity is regulated by a variety of signaling protein tyrosine kinase.
A 44-kDa extracellular signal-regulated MAP kinase that may play a role the initiation and regulation of MEIOSIS; MITOSIS; and postmitotic functions in differentiated cells. It phosphorylates a number of TRANSCRIPTION FACTORS; and MICROTUBULE-ASSOCIATED PROTEINS.
N-(1-Oxobutyl)-cyclic 3',5'-(hydrogen phosphate)-2'-butanoate guanosine. A derivative of cyclic GMP. It has a higher resistance to extracellular and intracellular phosphodiesterase than cyclic GMP.
A cyclic nucleotide phosphodiesterase subfamily that is found predominantly in inflammatory cells and may play a role in the regulation of CELL-MEDIATED IMMUNITY. The enzyme family includes over twenty different variants that occur due to multiple ALTERNATIVE SPLICING of the mRNA of at least four different genes.
A subgroup of mitogen-activated protein kinases that activate TRANSCRIPTION FACTOR AP-1 via the phosphorylation of C-JUN PROTEINS. They are components of intracellular signaling pathways that regulate CELL PROLIFERATION; APOPTOSIS; and CELL DIFFERENTIATION.
Intracellular signaling protein kinases that play a signaling role in the regulation of cellular energy metabolism. Their activity largely depends upon the concentration of cellular AMP which is increased under conditions of low energy or metabolic stress. AMP-activated protein kinases modify enzymes involved in LIPID METABOLISM, which in turn provide substrates needed to convert AMP into ATP.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
A potent cyclic nucleotide phosphodiesterase inhibitor; due to this action, the compound increases cyclic AMP and cyclic GMP in tissue and thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASES
A basic element found in nearly all organized tissues. It is a member of the alkaline earth family of metals with the atomic symbol Ca, atomic number 20, and atomic weight 40. Calcium is the most abundant mineral in the body and combines with phosphorus to form calcium phosphate in the bones and teeth. It is essential for the normal functioning of nerves and muscles and plays a role in blood coagulation (as factor IV) and in many enzymatic processes.
Established cell cultures that have the potential to propagate indefinitely.
Cells propagated in vitro in special media conducive to their growth. Cultured cells are used to study developmental, morphologic, metabolic, physiologic, and genetic processes, among others.
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
Compounds or agents that combine with an enzyme in such a manner as to prevent the normal substrate-enzyme combination and the catalytic reaction.
A protein kinase C subtype that was originally characterized as a CALCIUM-independent, serine-threonine kinase that is activated by PHORBOL ESTERS and DIACYLGLYCEROLS. It is targeted to specific cellular compartments in response to extracellular signals that activate G-PROTEIN-COUPLED RECEPTORS; TYROSINE KINASE RECEPTORS; and intracellular protein tyrosine kinase.
PKC beta encodes two proteins (PKCB1 and PKCBII) generated by alternative splicing of C-terminal exons. It is widely distributed with wide-ranging roles in processes such as B-cell receptor regulation, oxidative stress-induced apoptosis, androgen receptor-dependent transcriptional regulation, insulin signaling, and endothelial cell proliferation.
A subgroup of cyclic nucleotide-regulated ION CHANNELS within the superfamily of pore-loop cation channels. They are expressed in OLFACTORY NERVE cilia and in PHOTORECEPTOR CELLS and some PLANTS.
A PROTEIN-TYROSINE KINASE family that was originally identified by homology to the Rous sarcoma virus ONCOGENE PROTEIN PP60(V-SRC). They interact with a variety of cell-surface receptors and participate in intracellular signal transduction pathways. Oncogenic forms of src-family kinases can occur through altered regulation or expression of the endogenous protein and by virally encoded src (v-src) genes.
Enzymes that catalyze the hydrolysis of cyclic GMP to yield guanosine-5'-phosphate.
Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.
The process in which substances, either endogenous or exogenous, bind to proteins, peptides, enzymes, protein precursors, or allied compounds. Specific protein-binding measures are often used as assays in diagnostic assessments.
The insertion of recombinant DNA molecules from prokaryotic and/or eukaryotic sources into a replicating vehicle, such as a plasmid or virus vector, and the introduction of the resultant hybrid molecules into recipient cells without altering the viability of those cells.
Protein kinases that catalyze the PHOSPHORYLATION of TYROSINE residues in proteins with ATP or other nucleotides as phosphate donors.
A cyclic nucleotide derivative that mimics the action of endogenous CYCLIC AMP and is capable of permeating the cell membrane. It has vasodilator properties and is used as a cardiac stimulant. (From Merck Index, 11th ed)
The parts of a macromolecule that directly participate in its specific combination with another molecule.
A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC AMP. Several isoforms of the enzyme type exist, each with its own tissue localization. The isoforms are encoded by at least two genes and are a product of multiple alternative splicing of their mRNAs.
A heat-stable, low-molecular-weight activator protein found mainly in the brain and heart. The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl cyclase with subsequent activation. Thereby this protein modulates cyclic AMP and cyclic GMP levels.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Phosphoprotein with protein kinase activity that functions in the G2/M phase transition of the CELL CYCLE. It is the catalytic subunit of the MATURATION-PROMOTING FACTOR and complexes with both CYCLIN A and CYCLIN B in mammalian cells. The maximal activity of cyclin-dependent kinase 1 is achieved when it is fully dephosphorylated.
A cyclic nucleotide phosphodiesterase subfamily that is highly specific for CYCLIC GMP. It is found predominantly in vascular tissue and plays an important role in regulating VASCULAR SMOOTH MUSCLE contraction.
Inosine cyclic 3',5'-(hydrogen phosphate). An inosine nucleotide which acts as a mild inhibitor of the hydrolysis of cyclic AMP and cyclic GMP and as an inhibitor of cat heart cyclic AMP phosphodiesterase.
RNA sequences that serve as templates for protein synthesis. Bacterial mRNAs are generally primary transcripts in that they do not require post-transcriptional processing. Eukaryotic mRNA is synthesized in the nucleus and must be exported to the cytoplasm for translation. Most eukaryotic mRNAs have a sequence of polyadenylic acid at the 3' end, referred to as the poly(A) tail. The function of this tail is not known for certain, but it may play a role in the export of mature mRNA from the nucleus as well as in helping stabilize some mRNA molecules by retarding their degradation in the cytoplasm.
A ubiquitous casein kinase that is comprised of two distinct catalytic subunits and dimeric regulatory subunit. Casein kinase II has been shown to phosphorylate a large number of substrates, many of which are proteins involved in the regulation of gene expression.
An adenine nucleotide containing three phosphate groups esterified to the sugar moiety. In addition to its crucial roles in metabolism adenosine triphosphate is a neurotransmitter.
A multifunctional calcium-calmodulin-dependent protein kinase subtype that occurs as an oligomeric protein comprised of twelve subunits. It differs from other enzyme subtypes in that it lacks a phosphorylatable activation domain that can respond to CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE.
A long-acting derivative of cyclic AMP. It is an activator of cyclic AMP-dependent protein kinase, but resistant to degradation by cyclic AMP phosphodiesterase.
Domesticated bovine animals of the genus Bos, usually kept on a farm or ranch and used for the production of meat or dairy products or for heavy labor.
The uptake of naked or purified DNA by CELLS, usually meaning the process as it occurs in eukaryotic cells. It is analogous to bacterial transformation (TRANSFORMATION, BACTERIAL) and both are routinely employed in GENE TRANSFER TECHNIQUES.
Mitogen-activated protein kinase kinase kinases (MAPKKKs) are serine-threonine protein kinases that initiate protein kinase signaling cascades. They phosphorylate MITOGEN-ACTIVATED PROTEIN KINASE KINASES; (MAPKKs) which in turn phosphorylate MITOGEN-ACTIVATED PROTEIN KINASES; (MAPKs).
The degree of similarity between sequences of amino acids. This information is useful for the analyzing genetic relatedness of proteins and species.
Proteins prepared by recombinant DNA technology.
A methyl xanthine derivative from tea with diuretic, smooth muscle relaxant, bronchial dilation, cardiac and central nervous system stimulant activities. Theophylline inhibits the 3',5'-CYCLIC NUCLEOTIDE PHOSPHODIESTERASE that degrades CYCLIC AMP thus potentiates the actions of agents that act through ADENYLYL CYCLASES and cyclic AMP.
A dsRNA-activated cAMP-independent protein serine/threonine kinase that is induced by interferon. In the presence of dsRNA and ATP, the kinase autophosphorylates on several serine and threonine residues. The phosphorylated enzyme catalyzes the phosphorylation of the alpha subunit of EUKARYOTIC INITIATION FACTOR-2, leading to the inhibition of protein synthesis.
Identification of proteins or peptides that have been electrophoretically separated by blot transferring from the electrophoresis gel to strips of nitrocellulose paper, followed by labeling with antibody probes.
The relationship between the dose of an administered drug and the response of the organism to the drug.
A family of serine-threonine kinases that bind to and are activated by MONOMERIC GTP-BINDING PROTEINS such as RAC GTP-BINDING PROTEINS and CDC42 GTP-BINDING PROTEIN. They are intracellular signaling kinases that play a role the regulation of cytoskeletal organization.
A group of compounds with the heterocyclic ring structure of benzo(c)pyridine. The ring structure is characteristic of the group of opium alkaloids such as papaverine. (From Stedman, 25th ed)
A non-essential amino acid occurring in natural form as the L-isomer. It is synthesized from GLYCINE or THREONINE. It is involved in the biosynthesis of PURINES; PYRIMIDINES; and other amino acids.
The level of protein structure in which combinations of secondary protein structures (alpha helices, beta sheets, loop regions, and motifs) pack together to form folded shapes called domains. Disulfide bridges between cysteines in two different parts of the polypeptide chain along with other interactions between the chains play a role in the formation and stabilization of tertiary structure. Small proteins usually consist of only one domain but larger proteins may contain a number of domains connected by segments of polypeptide chain which lack regular secondary structure.
A single nucleotide variation in a genetic sequence that occurs at appreciable frequency in the population.
An abundant 43-kDa mitogen-activated protein kinase kinase subtype with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
Potent activator of the adenylate cyclase system and the biosynthesis of cyclic AMP. From the plant COLEUS FORSKOHLII. Has antihypertensive, positive inotropic, platelet aggregation inhibitory, and smooth muscle relaxant activities; also lowers intraocular pressure and promotes release of hormones from the pituitary gland.
A mitogen-activated protein kinase subfamily that is widely expressed and plays a role in regulation of MEIOSIS; MITOSIS; and post mitotic functions in differentiated cells. The extracellular signal regulated MAP kinases are regulated by a broad variety of CELL SURFACE RECEPTORS and can be activated by certain CARCINOGENS.
The biosynthesis of RNA carried out on a template of DNA. The biosynthesis of DNA from an RNA template is called REVERSE TRANSCRIPTION.
A family of protein serine/threonine kinases which act as intracellular signalling intermediates. Ribosomal protein S6 kinases are activated through phosphorylation in response to a variety of HORMONES and INTERCELLULAR SIGNALING PEPTIDES AND PROTEINS. Phosphorylation of RIBOSOMAL PROTEIN S6 by enzymes in this class results in increased expression of 5' top MRNAs. Although specific for RIBOSOMAL PROTEIN S6 members of this class of kinases can act on a number of substrates within the cell. The immunosuppressant SIROLIMUS inhibits the activation of ribosomal protein S6 kinases.
A deoxyribonucleotide polymer that is the primary genetic material of all cells. Eukaryotic and prokaryotic organisms normally contain DNA in a double-stranded state, yet several important biological processes transiently involve single-stranded regions. DNA, which consists of a polysugar-phosphate backbone possessing projections of purines (adenine and guanine) and pyrimidines (thymine and cytosine), forms a double helix that is held together by hydrogen bonds between these purines and pyrimidines (adenine to thymine and guanine to cytosine).
A protein-serine-threonine kinase that is activated by PHOSPHORYLATION in response to GROWTH FACTORS or INSULIN. It plays a major role in cell metabolism, growth, and survival as a core component of SIGNAL TRANSDUCTION. Three isoforms have been described in mammalian cells.
Products of proto-oncogenes. Normally they do not have oncogenic or transforming properties, but are involved in the regulation or differentiation of cell growth. They often have protein kinase activity.
A group of protein-serine-threonine kinases that was originally identified as being responsible for the PHOSPHORYLATION of CASEINS. They are ubiquitous enzymes that have a preference for acidic proteins. Casein kinases play a role in SIGNAL TRANSDUCTION by phosphorylating a variety of regulatory cytoplasmic and regulatory nuclear proteins.
Elements of limited time intervals, contributing to particular results or situations.
An enzyme of the lyase class that catalyzes the formation of CYCLIC AMP and pyrophosphate from ATP. EC
A mitogen-activated protein kinase kinase with specificity for JNK MITOGEN-ACTIVATED PROTEIN KINASES; P38 MITOGEN-ACTIVATED PROTEIN KINASES and the RETINOID X RECEPTORS. It takes part in a SIGNAL TRANSDUCTION pathway that is activated in response to cellular stress.
Protein kinases that control cell cycle progression in all eukaryotes and require physical association with CYCLINS to achieve full enzymatic activity. Cyclin-dependent kinases are regulated by phosphorylation and dephosphorylation events.
A phorbol ester found in CROTON OIL which, in addition to being a potent skin tumor promoter, is also an effective activator of calcium-activated, phospholipid-dependent protein kinase (protein kinase C). Due to its activation of this enzyme, phorbol 12,13-dibutyrate profoundly affects many different biological systems.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control of gene action in enzyme synthesis.
Inhibitor of phosphodiesterases.
Systems in which an intracellular signal is generated in response to an intercellular primary messenger such as a hormone or neurotransmitter. They are intermediate signals in cellular processes such as metabolism, secretion, contraction, phototransduction, and cell growth. Examples of second messenger systems are the adenyl cyclase-cyclic AMP system, the phosphatidylinositol diphosphate-inositol triphosphate system, and the cyclic GMP system.
Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. Intracellular signaling peptide and proteins may be part of an enzymatic signaling cascade or act through binding to and modifying the action of other signaling factors.
The sum of the weight of all the atoms in a molecule.
Cells grown in vitro from neoplastic tissue. If they can be established as a TUMOR CELL LINE, they can be propagated in cell culture indefinitely.
An indolocarbazole that is a potent PROTEIN KINASE C inhibitor which enhances cAMP-mediated responses in human neuroblastoma cells. (Biochem Biophys Res Commun 1995;214(3):1114-20)
Transport proteins that carry specific substances in the blood or across cell membranes.
Intracellular fluid from the cytoplasm after removal of ORGANELLES and other insoluble cytoplasmic components.
Recombinant proteins produced by the GENETIC TRANSLATION of fused genes formed by the combination of NUCLEIC ACID REGULATORY SEQUENCES of one or more genes with the protein coding sequences of one or more genes.
A specific protein kinase C inhibitor, which inhibits superoxide release from human neutrophils (PMN) stimulated with phorbol myristate acetate or synthetic diacylglycerol.
A strain of albino rat used widely for experimental purposes because of its calmness and ease of handling. It was developed by the Sprague-Dawley Animal Company.
Tumor-promoting compounds obtained from CROTON OIL (Croton tiglium). Some of these are used in cell biological experiments as activators of protein kinase C.
A transferase that catalyzes formation of PHOSPHOCREATINE from ATP + CREATINE. The reaction stores ATP energy as phosphocreatine. Three cytoplasmic ISOENZYMES have been identified in human tissues: the MM type from SKELETAL MUSCLE, the MB type from myocardial tissue and the BB type from nervous tissue as well as a mitochondrial isoenzyme. Macro-creatine kinase refers to creatine kinase complexed with other serum proteins.
A group of enzymes removing the SERINE- or THREONINE-bound phosphate groups from a wide range of phosphoproteins, including a number of enzymes which have been phosphorylated under the action of a kinase. (Enzyme Nomenclature, 1992)
The lipid- and protein-containing, selectively permeable membrane that surrounds the cytoplasm in prokaryotic and eukaryotic cells.
A phosphodiesterase 4 inhibitor with antidepressant properties.
Any of the processes by which nuclear, cytoplasmic, or intercellular factors influence the differential control (induction or repression) of gene action at the level of transcription or translation.
The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.
A group of enzymes that transfers a phosphate group onto an alcohol group acceptor. EC 2.7.1.
A serine-threonine protein kinase that, when activated by DNA, phosphorylates several DNA-binding protein substrates including the TUMOR SUPPRESSOR PROTEIN P53 and a variety of TRANSCRIPTION FACTORS.
Short sequences (generally about 10 base pairs) of DNA that are complementary to sequences of messenger RNA and allow reverse transcriptases to start copying the adjacent sequences of mRNA. Primers are used extensively in genetic and molecular biology techniques.
Benzopyrroles with the nitrogen at the number one carbon adjacent to the benzyl portion, in contrast to ISOINDOLES which have the nitrogen away from the six-membered ring.
The species Oryctolagus cuniculus, in the family Leporidae, order LAGOMORPHA. Rabbits are born in burrows, furless, and with eyes and ears closed. In contrast with HARES, rabbits have 22 chromosome pairs.
A glycogen synthase kinase that was originally described as a key enzyme involved in glycogen metabolism. It regulates a diverse array of functions such as CELL DIVISION, microtubule function and APOPTOSIS.
ATP:pyruvate 2-O-phosphotransferase. A phosphotransferase that catalyzes reversibly the phosphorylation of pyruvate to phosphoenolpyruvate in the presence of ATP. It has four isozymes (L, R, M1, and M2). Deficiency of the enzyme results in hemolytic anemia. EC
Theoretical representations that simulate the behavior or activity of biological processes or diseases. For disease models in living animals, DISEASE MODELS, ANIMAL is available. Biological models include the use of mathematical equations, computers, and other electronic equipment.
The fission of a CELL. It includes CYTOKINESIS, when the CYTOPLASM of a cell is divided, and CELL NUCLEUS DIVISION.
Nucleotides in which the base moiety is substituted with one or more sulfur atoms.
One of the mechanisms by which CELL DEATH occurs (compare with NECROSIS and AUTOPHAGOCYTOSIS). Apoptosis is the mechanism responsible for the physiological deletion of cells and appears to be intrinsically programmed. It is characterized by distinctive morphologic changes in the nucleus and cytoplasm, chromatin cleavage at regularly spaced sites, and the endonucleolytic cleavage of genomic DNA; (DNA FRAGMENTATION); at internucleosomal sites. This mode of cell death serves as a balance to mitosis in regulating the size of animal tissues and in mediating pathologic processes associated with tumor growth.
Proteins which bind to DNA. The family includes proteins which bind to both double- and single-stranded DNA and also includes specific DNA binding proteins in serum which can be used as markers for malignant diseases.
A cyclic AMP-dependent protein kinase subtype primarily found in particulate subcellular fractions. They are tetrameric proteins that contain two catalytic subunits and two type II-specific regulatory subunits.
Genetically engineered MUTAGENESIS at a specific site in the DNA molecule that introduces a base substitution, or an insertion or deletion.
Benzo-indoles similar to CARBOLINES which are pyrido-indoles. In plants, carbazoles are derived from indole and form some of the INDOLE ALKALOIDS.
A species of gram-negative, facultatively anaerobic, rod-shaped bacteria (GRAM-NEGATIVE FACULTATIVELY ANAEROBIC RODS) commonly found in the lower part of the intestine of warm-blooded animals. It is usually nonpathogenic, but some strains are known to produce DIARRHEA and pyogenic infections. Pathogenic strains (virotypes) are classified by their specific pathogenic mechanisms such as toxins (ENTEROTOXIGENIC ESCHERICHIA COLI), etc.
Highly conserved protein-serine threonine kinases that phosphorylate and activate a group of AGC protein kinases, especially in response to the production of the SECOND MESSENGERS, phosphatidylinositol 3,4,-biphosphate (PtdIns(3,4)P2) and phosphatidylinositol 3,4,5-triphosphate (PtdIns(3,4,5)P3).
An enzyme that catalyzes the conversion of GTP to 3',5'-cyclic GMP and pyrophosphate. It also acts on ITP and dGTP. (From Enzyme Nomenclature, 1992) EC
A class of cellular receptors that have an intrinsic PROTEIN-TYROSINE KINASE activity.
A cyclic GMP-dependent protein kinase subtype that is expressed in SMOOTH MUSCLE tissues and plays a role in regulation of smooth muscle contraction. Two isoforms, PKGIalpha and PKGIbeta, of the type I protein kinase exist due to alternative splicing of its mRNA.
A group of phenyl benzopyrans named for having structures like FLAVONES.
A non-essential amino acid. In animals it is synthesized from PHENYLALANINE. It is also the precursor of EPINEPHRINE; THYROID HORMONES; and melanin.
The muscle tissue of the HEART. It is composed of striated, involuntary muscle cells (MYOCYTES, CARDIAC) connected to form the contractile pump to generate blood flow.
Electrophoresis in which a polyacrylamide gel is used as the diffusion medium.
Isopropyl analog of EPINEPHRINE; beta-sympathomimetic that acts on the heart, bronchi, skeletal muscle, alimentary tract, etc. It is used mainly as bronchodilator and heart stimulant.
Purines attached to a RIBOSE and a phosphate that can polymerize to form DNA and RNA.
Compounds containing 1,3-diazole, a five membered aromatic ring containing two nitrogen atoms separated by one of the carbons. Chemically reduced ones include IMIDAZOLINES and IMIDAZOLIDINES. Distinguish from 1,2-diazole (PYRAZOLES).
A group of intracellular-signaling serine threonine kinases that bind to RHO GTP-BINDING PROTEINS. They were originally found to mediate the effects of rhoA GTP-BINDING PROTEIN on the formation of STRESS FIBERS and FOCAL ADHESIONS. Rho-associated kinases have specificity for a variety of substrates including MYOSIN-LIGHT-CHAIN PHOSPHATASE and LIM KINASES.
An essential amino acid occurring naturally in the L-form, which is the active form. It is found in eggs, milk, gelatin, and other proteins.
Linear POLYPEPTIDES that are synthesized on RIBOSOMES and may be further modified, crosslinked, cleaved, or assembled into complex proteins with several subunits. The specific sequence of AMINO ACIDS determines the shape the polypeptide will take, during PROTEIN FOLDING, and the function of the protein.
Protein factors that promote the exchange of GTP for GDP bound to GTP-BINDING PROTEINS.
A cell line derived from cultured tumor cells.
The part of CENTRAL NERVOUS SYSTEM that is contained within the skull (CRANIUM). Arising from the NEURAL TUBE, the embryonic brain is comprised of three major parts including PROSENCEPHALON (the forebrain); MESENCEPHALON (the midbrain); and RHOMBENCEPHALON (the hindbrain). The developed brain consists of CEREBRUM; CEREBELLUM; and other structures in the BRAIN STEM.
Single-stranded complementary DNA synthesized from an RNA template by the action of RNA-dependent DNA polymerase. cDNA (i.e., complementary DNA, not circular DNA, not C-DNA) is used in a variety of molecular cloning experiments as well as serving as a specific hybridization probe.
The first continuously cultured human malignant CELL LINE, derived from the cervical carcinoma of Henrietta Lacks. These cells are used for VIRUS CULTIVATION and antitumor drug screening assays.
An enzyme that catalyzes the conversion of ATP and thymidine to ADP and thymidine 5'-phosphate. Deoxyuridine can also act as an acceptor and dGTP as a donor. (From Enzyme Nomenclature, 1992) EC
Models used experimentally or theoretically to study molecular shape, electronic properties, or interactions; includes analogous molecules, computer-generated graphics, and mechanical structures.
Derivatives of the steroid androstane having two double bonds at any site in any of the rings.
Immunologic method used for detecting or quantifying immunoreactive substances. The substance is identified by first immobilizing it by blotting onto a membrane and then tagging it with labeled antibodies.
An enzyme that phosphorylates myosin light chains in the presence of ATP to yield myosin-light chain phosphate and ADP, and requires calcium and CALMODULIN. The 20-kDa light chain is phosphorylated more rapidly than any other acceptor, but light chains from other myosins and myosin itself can act as acceptors. The enzyme plays a central role in the regulation of smooth muscle contraction.
A c-jun amino-terminal kinase that is activated by environmental stress and pro-inflammatory cytokines. Several isoforms of the protein with molecular sizes of 43 and 48 KD exist due to multiple ALTERNATIVE SPLICING.
Cell lines whose original growing procedure consisted being transferred (T) every 3 days and plated at 300,000 cells per plate (J Cell Biol 17:299-313, 1963). Lines have been developed using several different strains of mice. Tissues are usually fibroblasts derived from mouse embryos but other types and sources have been developed as well. The 3T3 lines are valuable in vitro host systems for oncogenic virus transformation studies, since 3T3 cells possess a high sensitivity to CONTACT INHIBITION.
The region of an enzyme that interacts with its substrate to cause the enzymatic reaction.
Proteins which are found in membranes including cellular and intracellular membranes. They consist of two types, peripheral and integral proteins. They include most membrane-associated enzymes, antigenic proteins, transport proteins, and drug, hormone, and lectin receptors.
Guanosine 5'-(tetrahydrogen triphosphate). A guanine nucleotide containing three phosphate groups esterified to the sugar moiety.
A protein serine-threonine kinase that catalyzes the PHOSPHORYLATION of I KAPPA B PROTEINS. This enzyme also activates the transcription factor NF-KAPPA B and is composed of alpha and beta catalytic subunits, which are protein kinases and gamma, a regulatory subunit.
Compounds with a six membered aromatic ring containing NITROGEN. The saturated version is PIPERIDINES.
The phenotypic manifestation of a gene or genes by the processes of GENETIC TRANSCRIPTION and GENETIC TRANSLATION.
The relationship between the chemical structure of a compound and its biological or pharmacological activity. Compounds are often classed together because they have structural characteristics in common including shape, size, stereochemical arrangement, and distribution of functional groups.
Compounds or factors that act on a specific enzyme to increase its activity.
Extrachromosomal, usually CIRCULAR DNA molecules that are self-replicating and transferable from one organism to another. They are found in a variety of bacterial, archaeal, fungal, algal, and plant species. They are used in GENETIC ENGINEERING as CLONING VECTORS.
Endogenous substances, usually proteins, which are effective in the initiation, stimulation, or termination of the genetic transcription process.
The sequential correspondence of nucleotides in one nucleic acid molecule with those of another nucleic acid molecule. Sequence homology is an indication of the genetic relatedness of different organisms and gene function.
A species of the genus SACCHAROMYCES, family Saccharomycetaceae, order Saccharomycetales, known as "baker's" or "brewer's" yeast. The dried form is used as a dietary supplement.
The phosphoric acid ester of serine.
Organic nitrogenous bases. Many alkaloids of medical importance occur in the animal and vegetable kingdoms, and some have been synthesized. (Grant & Hackh's Chemical Dictionary, 5th ed)
A family of ribosomal protein S6 kinases that are structurally distinguished from RIBOSOMAL PROTEIN S6 KINASES, 70-KDA by their apparent molecular size and the fact they contain two functional kinase domains. Although considered RIBOSOMAL PROTEIN S6 KINASES, members of this family are activated via the MAP KINASE SIGNALING SYSTEM and have been shown to act on a diverse array of substrates that are involved in cellular regulation such as RIBOSOMAL PROTEIN S6 and CAMP RESPONSE ELEMENT-BINDING PROTEIN.
Serologic tests in which a positive reaction manifested by visible CHEMICAL PRECIPITATION occurs when a soluble ANTIGEN reacts with its precipitins, i.e., ANTIBODIES that can form a precipitate.
DNA sequences which are recognized (directly or indirectly) and bound by a DNA-dependent RNA polymerase during the initiation of transcription. Highly conserved sequences within the promoter include the Pribnow box in bacteria and the TATA BOX in eukaryotes.
Proteins that control the CELL DIVISION CYCLE. This family of proteins includes a wide variety of classes, including CYCLIN-DEPENDENT KINASES, mitogen-activated kinases, CYCLINS, and PHOSPHOPROTEIN PHOSPHATASES as well as their putative substrates such as chromatin-associated proteins, CYTOSKELETAL PROTEINS, and TRANSCRIPTION FACTORS.
A 195-kDa MAP kinase kinase kinase with broad specificity for MAP KINASE KINASES. It is found localized in the CYTOSKELETON and can activate a variety of MAP kinase-dependent pathways.
An enzyme that catalyzes the conversion of phosphatidylinositol (PHOSPHATIDYLINOSITOLS) to phosphatidylinositol 4-phosphate, the first committed step in the biosynthesis of phosphatidylinositol 4,5-bisphosphate.
A family of cell cycle-dependent kinases that are related in structure to CDC28 PROTEIN KINASE; S CEREVISIAE; and the CDC2 PROTEIN KINASE found in mammalian species.
An enzyme of the transferase class that uses ATP to catalyze the phosphorylation of diacylglycerol to a phosphatidate. EC
A family of highly conserved serine-threonine kinases that are involved in the regulation of MITOSIS. They are involved in many aspects of cell division, including centrosome duplication, SPINDLE APPARATUS formation, chromosome alignment, attachment to the spindle, checkpoint activation, and CYTOKINESIS.
Within a eukaryotic cell, a membrane-limited body which contains chromosomes and one or more nucleoli (CELL NUCLEOLUS). The nuclear membrane consists of a double unit-type membrane which is perforated by a number of pores; the outermost membrane is continuous with the ENDOPLASMIC RETICULUM. A cell may contain more than one nucleus. (From Singleton & Sainsbury, Dictionary of Microbiology and Molecular Biology, 2d ed)
A cyclic nucleotide formed from CYTIDINE TRIPHOSPHATE by the action of cytidylate cyclase. It is a potential cyclic nucleotide intracellular mediator of signal transductions.
A large lobed glandular organ in the abdomen of vertebrates that is responsible for detoxification, metabolism, synthesis and storage of various substances.
A 44 kDa mitogen-activated protein kinase kinase with specificity for MITOGEN-ACTIVATED PROTEIN KINASE 1 and MITOGEN-ACTIVATED PROTEIN KINASE 3.
Adenine nucleotide containing one phosphate group esterified to the sugar moiety in the 2'-, 3'-, or 5'-position.
Connective tissue cells which secrete an extracellular matrix rich in collagen and other macromolecules.
A subfamily in the family MURIDAE, comprising the hamsters. Four of the more common genera are Cricetus, CRICETULUS; MESOCRICETUS; and PHODOPUS.
Components of a cell produced by various separation techniques which, though they disrupt the delicate anatomy of a cell, preserve the structure and physiology of its functioning constituents for biochemical and ultrastructural analysis. (From Alberts et al., Molecular Biology of the Cell, 2d ed, p163)
Gated, ion-selective glycoproteins that traverse membranes. The stimulus for ION CHANNEL GATING can be due to a variety of stimuli such as LIGANDS, a TRANSMEMBRANE POTENTIAL DIFFERENCE, mechanical deformation or through INTRACELLULAR SIGNALING PEPTIDES AND PROTEINS.
A subgroup of cyclic nucleotide-regulated ION CHANNELS of the superfamily of pore-loop cation channels that are opened by hyperpolarization rather than depolarization. The ion conducting pore passes SODIUM, CALCIUM, and POTASSIUM cations with a preference for potassium.
A negative regulatory effect on physiological processes at the molecular, cellular, or systemic level. At the molecular level, the major regulatory sites include membrane receptors, genes (GENE EXPRESSION REGULATION), mRNAs (RNA, MESSENGER), and proteins.
A subclass of phospholipases that hydrolyze the phosphoester bond found in the third position of GLYCEROPHOSPHOLIPIDS. Although the singular term phospholipase C specifically refers to an enzyme that catalyzes the hydrolysis of PHOSPHATIDYLCHOLINE (EC, it is commonly used in the literature to refer to broad variety of enzymes that specifically catalyze the hydrolysis of PHOSPHATIDYLINOSITOLS.
A variation of the PCR technique in which cDNA is made from RNA via reverse transcription. The resultant cDNA is then amplified using standard PCR protocols.
A metallic element that has the atomic symbol Mg, atomic number 12, and atomic weight 24.31. It is important for the activity of many enzymes, especially those involved in OXIDATIVE PHOSPHORYLATION.
Nucleotides in which the purine or pyrimidine base is combined with ribose. (Dorland, 28th ed)

Kinase phosphorylation: Keeping it all in the family. (1/7)

The identification of PDK1 as a kinase that phosphorylates the AGC family of kinases led to a hunt for 'PDK2', a hypothetical regulated kinase(s) that would be required for full activation of the AGC kinases. Recent findings suggest that the elusive PDK2 may actually be a familiar kinase with an atypical associate.  (+info)

Phosphorylation of type-1 inositol 1,4,5-trisphosphate receptors by cyclic nucleotide-dependent protein kinases: a mutational analysis of the functionally important sites in the S2+ and S2- splice variants. (2/7)

Inositol 1,4,5-trisphosphate receptors (InsP3R) are the major route of intracellular calcium release in eukaryotic cells and as such are pivotal for stimulation of Ca2+-dependent effectors important for numerous physiological processes. Modulation of this release has important consequences for defining the particular spatio-temporal characteristics of Ca2+ signals. In this study, regulation of Ca2+ release by phosphorylation of type-1 InsP3R (InsP3R-1) by cAMP (PKA)- and cGMP (PKG)-dependent protein kinases was investigated in the two major splice variants of InsP3R-1. InsP3R-1 was expressed in DT-40 cells devoid of endogenous InsP3R. In cells expressing the neuronal, S2+ splice variant of the InsP3R-1, Ca2+ release was markedly enhanced when either PKA or PKG was activated. The sites of phosphorylation were investigated by mutation of serine residues present in two canonical phosphorylation sites present in the protein. Potentiated Ca2+ release was abolished when serine 1755 was mutated to alanine (S1755A) but was unaffected by a similar mutation of serine 1589 (S1589A). These data demonstrate that Ser-1755 is the functionally important residue for phosphoregulation by PKA and PKG in the neuronal variant of the InsP3R-1. Activation of PKA also resulted in potentiated Ca2+ release in cells expressing the non-neuronal, S2- splice variant of the InsP3R-1. However, the PKA-induced potentiation was still evident in S1589A or S1755A InsP3R-1 mutants. The effect was abolished in the double (S1589A/S1755A) mutant, indicating both sites are phosphorylated and contribute to the functional effect. Activation of PKG had no effect on Ca2+ release in cells expressing the S2- variant of InsP3R-1. Collectively, these data indicate that phosphoregulation of InsP3R-1 has dramatic effects on Ca2+ release and defines the molecular sites phosphorylated in the major variants expressed in neuronal and peripheral tissues.  (+info)

Ca(2+)-dependent conformational changes in guanylyl cyclase-activating protein 2 (GCAP-2) revealed by site-specific phosphorylation and partial proteolysis. (3/7)

Guanylyl cyclase-activating proteins (GCAPs) are calcium sensor proteins of the EF-hand superfamily that inhibit retinal photoreceptor membrane guanylyl cyclase (retGC) in the dark when they bind Ca(2+) but activate retGC when Ca(2+) dissociates from GCAPs in response to light stimulus. We addressed the difference in exposure of GCAP-2 structure to protein kinase and a protease as indicators of conformational change caused by binding and release of Ca(2+). We have found that unlike its homolog, GCAP-1, the C terminus of GCAP-2 undergoes phosphorylation by cyclic nucleotide-dependent protein kinases (CNDPK) present in the retinal extract and rapid dephosphorylation by the protein phosphatase PP2C present in the retina. Inactivation of the CNDPK phosphorylation site in GCAP-2 by substitutions S201G or S201D, as well as phosphorylation or thiophosphorylation of Ser(201), had little effect on the ability of GCAP-2 to regulate retGC in reconstituted membranes in vitro. At the same time, Ca(2+) strongly inhibited phosphorylation of the wild-type GCAP-2 by retinal CNDPK but did not affect phosphorylation of a constitutively active Ca(2+)-insensitive GCAP-2 mutant. Partial digestion of purified GCAP-2 with Glu-C protease revealed at least two sites that become exposed or constrained in a Ca(2+)-sensitive manner. The Ca(2+)-dependent conformational changes in GCAP-2 affect the areas around Glu(62) residue in the entering helix of EF-hand 2, the areas proximal to the exiting helix of EF-hand 3, and Glu(136)-Glu (138) between EF-hand 3 and EF-hand 4. These changes also cause the release of the C-terminal Ser(201) from the constraint caused by the Ca(2+)-bound conformation.  (+info)

KMUP-1 activates BKCa channels in basilar artery myocytes via cyclic nucleotide-dependent protein kinases. (4/7)

This study investigated whether KMUP-1, a synthetic xanthine-based derivative, augments the delayed-rectifier potassium (K(DR))- or large-conductance Ca2+-activated potassium (BKCa) channel activity in rat basilar arteries through protein kinase-dependent and -independent mechanisms. Cerebral smooth muscle cells were enzymatically dissociated from rat basilar arteries. Conventional whole cell, perforated and inside-out patch-clamp electrophysiology was used to monitor K+- and Ca2+ channel activities. KMUP-1 (1 microM) had no effect on the K(DR) current but dramatically enhanced BKCa channel activity. This increased BKCa current activity was abolished by charybdotoxin (100 nM) and iberiotoxin (100 nM). Like KMUP-1, the membrane-permeable analogs of cGMP (8-Br-cGMP) and cAMP (8-Br-cAMP) enhanced the BKCa current. BKCa current activation by KMUP-1 was markedly inhibited by a soluble guanylate cyclase inhibitor (ODQ 10 microM), an adenylate cyclase inhibitor (SQ 22536 10 microM), competitive antagonists of cGMP and cAMP (Rp-cGMP, 100 microM and Rp-cAMP, 100 microM), and cGMP- and cAMP-dependent protein kinase inhibitors (KT5823, 300 nM and KT5720, 300 nM). Voltage-dependent L-type Ca2+ current was significantly suppressed by KMUP-1 (1 microM), and nearly abolished by a calcium channel blocker (nifedipine, 1 microM). In conclusion, KMUP-1 stimulates BKCa currents by enhancing the activity of cGMP-dependent protein kinase, and in part this is due to increasing cAMP-dependent protein kinase. Physiologically, this activation would result in the closure of voltage-dependent calcium channels and the relaxation of cerebral arteries.  (+info)

Osmotic regulation of betaine homocysteine-S-methyltransferase expression in H4IIE rat hepatoma cells. (5/7)

Cell hydration changes critically affect liver metabolism and gene expression. In the course of gene expression studies using nylon cDNA-arrays we found that hyperosmolarity (405 mosmol/l) suppressed the betaine-homocysteine methyltransferase (Bhmt) mRNA expression in H4IIE rat hepatoma cells. This was confirmed by Northern blot and real-time quantitative RT-PCR analysis, which in addition unraveled a pronounced induction of Bhmt mRNA expression by hypoosmotic (205 mosmol/l) swelling. Osmotic regulation of Bhmt mRNA expression was largely paralleled at the levels of Bhmt protein and enzymatic activity. Like hyperosmotic NaCl, hyperosmotic raffinose but not hyperosmotic urea suppressed Bhmt mRNA expression, suggesting that cell shrinkage rather than increased ionic strength or hyperosmolarity per se is the trigger. Hypoosmolarity increased the expression of a reporter gene driven by the entire human BHMT promoter, whereas destabilization of BHMT mRNA was observed under hyperosmotic conditions. Osmosensitivity of Bhmt mRNA expression was impaired by inhibitors of tyrosine kinases and cyclic nucleotide-dependent kinases. The osmotic regulation of BHMT may be part of a cell volume-regulatory response and additionally lead to metabolic alterations that depend on the availability of betaine-derived methyl groups.  (+info)

Berberine and its more biologically available derivative, dihydroberberine, inhibit mitochondrial respiratory complex I: a mechanism for the action of berberine to activate AMP-activated protein kinase and improve insulin action. (6/7)


Alcohol stimulates ciliary motility of isolated airway axonemes through a nitric oxide, cyclase, and cyclic nucleotide-dependent kinase mechanism. (7/7)


Intracellular cAMP and cGMP levels are increased in response to a variety of hormonal and chemical stimuli; these nucleotides play key roles as second messenger signals in modulating myriad physiological processes. The cAMP-dependent protein kinase and cGMP-dependent protein kinase are major intrace …
A comparative analysis on protein kinases encoded in the completely sequenced genomes of two plant species, namely Arabidopsis thaliana and Oryza sativa spp japonica cv. Nipponbare is reported in the current study. We have analysed 836 and 1386 kinases identified from A. thaliana and the $O$. sativa genomes respectively. Their classification into known subfamilies reveals selective expansions of the plant receptor kinase subfamily comprising of Ser/Thr receptor kinases. The presence of calciumdependent kinases, and potential absence of cyclic nucleotide-dependent protein kinase of the type found in other (non-plant) eukaryotes, are other notable features of the two plant kinomes described here. An analysis on domain organisation of each of the protein kinases encoded in the plant genome has been carried out. Uncommon composition of functional domains like nuclear translocation factor domain, redox sensor domain (PAS), ACT and lectin domains are observed in few protein kinases shared between the ...
Welcome to the weekly Orientation for The Career Center (NYC). Please bring your card with you if you are a member of an entertainment union. Orientation for The Career Center (NYC) is held every Monday at 12 nn and some Monday evenings at 5 pm.. ...
Background: Hemostasis is a critical and active function of the blood mediated by platelets. Therefore, the prevention of pathological platelet aggregation is of great importance as well as of pharmaceutical and medical interest. Endogenous platelet inhibition is predominantly based on cyclic nucleotides (cAMP, cGMP) elevation and subsequent cyclic nucleotide-dependent protein kinase (PKA, PKG) activation. In turn, platelet phosphodiesterases (PDEs) and protein phosphatases counterbalance their activity. This main inhibitory pathway in human platelets is crucial for countervailing unwanted platelet activation. Consequently, the regulators of cyclic nucleotide signaling are of particular interest to pharmacology and therapeutics of atherothrombosis. Modeling of pharmacodynamics allows understanding this intricate signaling and supports the precise description of these pivotal targets for pharmacological modulation. Results: We modeled dynamically concentration-dependent responses of pathway ...
annotations (the reliablity of the annotated protein expression using immunohistochemically (IH) stained on human tissues, the reliablity of the annotated protein expression in immunofluorescently (IF) stained human cell lines, tissue specificity (the distribution of antibody staining or protein expression in human cell types), cell line specificity (the distribution of RNA abundance in cell lines) and subcellular location (based on immunofluorescent staining of cell lines ...
For years, scientists have been in disagreement as to whether the amyloid plaques cause Alzheimers disease or whether they are a byproduct of some other process. This is the first animal model to show that amyloid and deficits in learning and memory are associated, says D. Stephen Snyder, Ph.D., Program Director, Etiology of Alzheimers Disease, NIA. However, whether the deficits are caused by or merely correlate with the presence of amyloid remains unresolved. Further testing with this model may help us understand the relationship between plaques and behavior, something we need to know for the development of effective drug therapies ...
This project collected, examined, and analyzed 217 fish representing three species at 10 stations in the U.S. portion of the Yukon River Basin (YRB) from May to October 2002. Four sampling sites were located on the Yukon River; two were located on the Porcupine River, and one site was on each of the Ray, Tanana, Tolavana, and Innoko Rivers. Norther pike (Esox lucius), longnose sucker (Catostomus catostomus), and burbot (Lota lota) were weighed and measured, and examined in the field for external and internal lesions, and liver, spleen, and gonads were weighed to compute somatic indices. Selected tissues and fluids were collected and preserved for analysis of fish health and reproductive biomarkers. Composite samples of whole fish from each station were grouped by species and gender and analyzed for organochlorines and elemental contaminants and for dioxin-like activity using H4IIE rat hepatoma cell bioassay....
Nitrogenase is a complex metal-containing enzyme that catalyzes the conversion of nitrogen gas to ammonia. During nitrogenase catalysis the Fe protein and the molybdenum-iron protein associate and dissociate in a manner resulting in the hydrolysis of two molecules of MgATP and the transfer of at least one electron to the MoFe protein. The role of nucleotide binding and hydrolysis in nitrogenase catalysis is one of the most fascinating aspects of nitrogenase function. The Fe protein upon binding to MgATP undergoes a huge conformational change which is important for subsequent steps of nitrogenase reaction mechanism. Therefore structural characterization of the Fe protein bound to MgATP will provide a basis on how MgATP binding promotes the complex formation whereas hydrolysis to MgADP leads to the dissociation of the macromolecular complex structure. Towards these ends we have conducted structural studies on a site-directed variant of the Fe protein which is a close mimic of the MgATP ...
The concentration of guanosine 3′,5′-monophosphate (cGMP) controls the response to light in the retina. Binding of cGMP to a plasma membrane cation channel maintains a small calcium flux. Light promotes the degradation of cGMP, allowing these cyclic nucleotide-gated channels to close, resulting in hyperpolarization and a fall in intracellular calcium concentration. Production of cGMP is intimately associated with this changing calcium concentration such that when calcium is high, guanylyl cyclase-activating proteins (GCAPs) inhibit guanylate cyclase (GC) activity, and when calcium is low, GCAPs activate GC activity. However, in vitro the responsiveness of GCAPs to calcium is outside the range of calcium concentrations present in the retina. Peshenko and Dizhoor report that the Mg2+ concentration sets the dynamic range of calcium concentrations over which GCAPs regulate GC activity in assays with recombinant GCAP and outer segment membranes or mouse retina homogenate. Tryptophan fluorescence ...
Biology (11th Edition) answers to Chapter 50 - Osmotic Regulation and the Urinary System - Review Questions - Synthesize 1b including work step by step written by community members like you. Textbook Authors: Raven, Peter; Johnson, George; Mason, Kenneth; Losos, Jonathan; Singer, Susan , ISBN-10: 1-25918-813-2, ISBN-13: 978-1-25918-813-8, Publisher: McGraw-Hill Education
"Protein phosphorylation regulated by cyclic nucleotide-dependent protein kinases in cell extracts and in intact human ... VASP is regulated by the cyclic nucleotide-dependent kinases PKA and PKG. Vasodilator-stimulated phosphoprotein has been shown ... "The vasodilator-stimulated phosphoprotein is regulated by cyclic GMP-dependent protein kinase during neutrophil spreading". J. ... 2000). "Fyn-binding protein (Fyb)/SLP-76-associated protein (SLAP), Ena/vasodilator-stimulated phosphoprotein (VASP) proteins ...
While protein kinase A (PKA) or cAMP-dependent protein kinase and cyclic nucleotide regulated ion channel (CNG and HCN) were ... opposing effects of exchange protein directly activated by cyclic AMP and cAMP-dependent protein kinase on protein kinase B ... or cAMP-regulated guanine nucleotide exchange factor I (cAMP-GEFI) is a protein that in humans is encoded by the RAPGEF3 gene. ... "The protein kinase A anchoring protein mAKAP coordinates two integrated cAMP effector pathways". Nature. 437 (7058): 574-8. doi ...
... cyclic nucleotide-regulated protein kinases MeSH D12.644.360.200.125 - cyclic amp-dependent protein kinases MeSH D12.644. ... map kinase kinase kinase 1 MeSH D12.644.360.400.200 - map kinase kinase kinase 2 MeSH D12.644.360.400.300 - map kinase kinase ... kinase 3 MeSH D12.644.360.400.400 - map kinase kinase kinase 4 MeSH D12.644.360.400.500 - map kinase kinase kinase 5 MeSH ... mitogen-activated protein kinase kinases MeSH D12.644.360.440.100 - map kinase kinase 1 MeSH D12.644.360.440.200 - map kinase ...
... acts as a second messenger by interacting with and regulating other proteins such as protein kinase A and cyclic nucleotide- ... Adenylyl cyclase is regulated by G proteins, which can be found in the monomeric form or the heterotrimeric form, consisting of ... Soluble AC (sAC) is not a transmembrane form and is not regulated by G proteins or forskolin, instead acts as a bicarbonate/pH ... Beta adrenergic receptor kinase pathway "PDB101: Molecule of the Month: G Proteins". RCSB: PDB-101. Retrieved 24 August 2020. ...
... binds to and regulates the function of ion channels such as the HCN channels and a few other cyclic nucleotide-binding proteins ... Not all protein kinases respond to cAMP. Several classes of protein kinases, including protein kinase C, are not cAMP-dependent ... In eukaryotes, cyclic AMP works by activating protein kinase A (PKA, or cAMP-dependent protein kinase). PKA is normally ... It should not be confused with 5'-AMP-activated protein kinase (AMP-activated protein kinase). Earl Sutherland of Vanderbilt ...
Betz H., Changeux J.-P. (1979). Regulation of muscle acetylcholine receptor synthesis in vitro by cyclic nucleotide derivatives ... involvement of protein kinase C and Ca++. Neuron 2: 1229-1236. Piette J., Bessereau J.-L., Huchet M., Changeux J.-P. (1990). ... The group also discovered that the nicotinic receptor is regulated by a variety of "allosteric modulators" such as: 1. calcium ... from the structure and function of proteins (with a focus on the allosteric proteins), to the early development of the nervous ...
"Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase". The Journal ... Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/ ... "Myomegalin is a novel protein of the golgi/centrosome that interacts with a cyclic nucleotide phosphodiesterase". The Journal ... Hoffmann R, Baillie GS, MacKenzie SJ, Yarwood SJ, Houslay MD (Feb 1999). "The MAP kinase ERK2 inhibits the cyclic AMP-specific ...
Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/ ... It is named for its ability to catalyze the phosphodiester hydrolysis of 2',3'-cyclic nucleotides to 2'-nucleotides, though a ... Cyclic nucleotide 3'-phosphodiesterase: a membrane-bound, microtubule-associated protein and membrane anchor for tubulin". ... Cyclic nucleotide 3'-phosphodiesterase: a membrane-bound, microtubule-associated protein and membrane anchor for tubulin". ...
G-protein-coupled receptor kinase 2) D2 dopamine receptor IL1RAPL1 (interleukin-1 receptor accessory protein-like 1 protein) ... cyclic nucleotide phosphodiesterases ARF1 (ADP Ribosylation factor 1) A type (Kv4.3; Shal-related subfamily, member 3) voltage- ... NCS-1 regulates synaptic transmission, helps control the dynamics of nerve terminal growth, is critical for some forms of ... It is the Ca2+-sensing subunit of the yeast phosphatidylinositol (PtdIns)-4-OH kinase, PIK1 It binds to many proteins, some in ...
These small molecules bind and activate protein kinases, ion channels, and other proteins, thus continuing the signaling ... the cyclases that synthesize cyclic nucleotides, or by opening of ion channels to allow influx of metal ions, for example Ca2+ ... from the plasma membrane into the intermembrane space where they can reach and regulate membrane-associated effector proteins. ... In the case of G protein-coupled receptors, the conformation change exposes a binding site for a G-protein. The G-protein ( ...
... calmodulin-regulated, 3',5'-cyclic nucleotide phosphodiesterases". J Biol Chem. 271 (2): 796-806. doi:10.1074/jbc.271.2.796. ... Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/ ... 2007). "Cyclic nucleotide phosphodiesterase PDE1C1 in human cardiac myocytes". J. Biol. Chem. 282 (45): 32749-57. doi:10.1074/ ... Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1C is an enzyme that in humans is encoded by the PDE1C ...
The protein encoded by this gene belongs to the cyclic nucleotide phosphodiesterase (PDE) family, and PDE4 subfamily. This PDE ... Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/ ... Thus, by regulating the cellular concentration of cAMP, this protein plays a key role in many important physiological processes ... Zhou L, Thompson WJ, Potter DE (Jul 1999). "Multiple cyclic nucleotide phosphodiesterases in human trabecular meshwork cells" ( ...
Cell Biol., 1 (5): 305-311, doi:10.1038/13024, PMID 10559944 Scott, J. D. (1991), "Cyclic nucleotide-dependent protein kinases ... "PTP-SL and STEP protein tyrosine phosphatases regulate the activation of the extracellular signal-regulated kinases ERK1 and ... 1993), "Protein kinase A antagonizes platelet-derived growth factor-induced signaling by mitogen-activated protein kinase in ... 1996), "Cyclic AMP-dependent protein kinase (cAK) in human B cells: co-localization of type I cAK (RIα2C2) with the antigen ...
Glavas NA, Ostenson C, Schaefer JB, Vasta V, Beavo JA (2001). "T cell activation up-regulates cyclic nucleotide ... Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/ ... Mammals possess 21 cyclic nucleotide phosphodiesterase (PDE) genes that are pharmacologically grouped into 11 families. PDE7A ... Wang H, Liu Y, Chen Y, Robinson H, Ke H (2005). "Multiple elements jointly determine inhibitor selectivity of cyclic nucleotide ...
... and are often specific to a single protein or class of proteins with which they interact. Nucleoside-diphosphate kinase Guanine ... "Epidermal growth factor regulates p21ras through the formation of a complex of receptor, Grb2 adapter protein, and Sos ... nucleotide-exchange factor directly activated by cyclic AMP" (PDF). Nature. 396 (6710): 474-477. Bibcode:1998Natur.396..474D. ... Play media Nucleotide exchange factors (NEFs) are proteins that stimulate the exchange (replacement) of nucleoside diphosphates ...
Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/ ... 1999). "Isolation and characterization of PDE10A, a novel human 3', 5'-cyclic nucleotide phosphodiesterase". Gene. 234 (1): 109 ... and cGMP-mediated intracellular signaling by hydrolyzing the cyclic nucleotide to the corresponding nucleoside 5-prime ... cAMP and cAMP-inhibited cGMP 3',5'-cyclic phosphodiesterase 10A is an enzyme that in humans is encoded by the PDE10A gene. ...
Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/ ... Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1B is an enzyme that in humans is encoded by the PDE1B ... 1992). "A polymerase chain reaction strategy to identify and clone cyclic nucleotide phosphodiesterase cDNAs. Molecular cloning ... Bender AT, Beavo JA (2006). "PDE1B2 regulates cGMP and a subset of the phenotypic characteristics acquired upon macrophage ...
This activity is dependent on AtPEPR 1 and cyclic nucleotide gated channel 2 (CNGC2) . Activation of CNGC2 occurs through cGMP ... Ryan CA, Pearce G (November 2003). "Systemins: a functionally defined family of peptide signals that regulate defensive genes ... Leucine-rich repeat receptor like protein kinase (PEPR1 and PEPR2 in Arabidopsis thaliana and Xa21 in rice) are plant cell ... Plant membrane PRR mainly consist of receptor like kinases and receptor like proteins. They sense PAMPs such as chitin from ...
... which resultes in the activation of protein kinase A (PKA) and is known to activate CREB by the mitogen-activated protein ... It has been shown in studies that transport of HCN (hyperpolarization activated cyclic nucleotide) gated channel isoforms to ... Among the signals studied in this system is CaMKII a calcium/calmodulin-regulated serine/threonine kinase which is required for ... However, in all areas, dendritic synthesis of proteins is necessary for late long-term potentials in the hippocampal neurons. ...
PDE3A and PDE3B activity is regulated by several phosphorylation pathways. Protein kinase A and Protein kinase B both activate ... Aggregation of platelets is highly regulated by cyclic nucleotides. PDE3A is a regulator of this process, and PDE3 inhibitors ... Activation of PDE3B decreases concentrations of cAMP, which in turn reduces Protein kinase A activity. Protein kinase A is ... The proposed molecular mechanism of cyclic nucleotide specificity of PDEs is the so-called glutamine switch mechanism. In the ...
... concentration of the second messenger cAMP may lead to the activation of cyclic nucleotide-gated ion channels exchange proteins ... In humans, cAMP works by activating protein kinase A (PKA, cAMP-dependent protein kinase), one of the first few kinases ... This pathway can activate enzymes and regulate gene expression. The activation of preexisting enzymes is a much faster process ... Further effects mainly depend on cAMP-dependent protein kinase, which vary based on the type of cell. cAMP-dependent pathway is ...
CRP proteins function as cyclic nucleotide-regulated transcription factors that modulate the expression of genes encoding ... Significant structural similarity is evident between the Popeye domain and cAMP binding domains of eukaryotic protein kinase A ... The cyclic AMP-binding domains of these proteins display approximately 25% identity and 60% similarity to the Popeye domain. ... The Popeye domain binds cyclic nucleotides and has a binding affinity (IC50) for cAMP of 120 nM, which is comparable to the ...
Potassium/sodium hyperpolarization-activated cyclic nucleotide-gated channel 4 is a protein that in humans is encoded by the ... Nomenclature and structure-function relationships of cyclic nucleotide-regulated channels". Pharmacological Reviews. 57 (4): ... "Phosphorylation and modulation of hyperpolarization-activated HCN4 channels by protein kinase A in the mouse sinoatrial node". ... Cyclic nucleotide-gated ion channel Funny current GRCh38: Ensembl release 89: ENSG00000138622 - Ensembl, May 2017 GRCm38: ...
Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/ ... cyclic nucleotides cAMP and cGMP function as second messengers in a wide variety of signal transduction pathways. 3',5'-cyclic ... Loughney K, Taylor J, Florio VA (2005). "3',5'-cyclic nucleotide phosphodiesterase 11A: localization in human tissues". Int. J ... Yuasa K, Ohgaru T, Asahina M, Omori K (2001). "Identification of rat cyclic nucleotide phosphodiesterase 11A (PDE11A): ...
... calmodulin-regulated, 3',5'-cyclic nucleotide phosphodiesterases". J Biol Chem. 271 (2): 796-806. doi:10.1074/jbc.271.2.796. ... Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/ ... Calcium/calmodulin-dependent 3',5'-cyclic nucleotide phosphodiesterase 1A is an enzyme that in humans is encoded by the PDE1A ... Lefièvre L, de Lamirande E, Gagnon C (2003). "Presence of cyclic nucleotide phosphodiesterases PDE1A, existing as a stable ...
... activate cyclic nucleotide-gated ion channels in the olfactory system. GTP-gamma-S GDPCP G protein G protein-coupled receptor 5 ... The importing of these proteins plays an important role in several pathways regulated within the mitochondria organelle, such ... since GTP is readily converted to ATP with nucleoside-diphosphate kinase (NDK). During the elongation stage of translation, GTP ... Cyclic guanosine triphosphate (cGTP) helps cyclic adenosine monophosphate (cAMP) ...
Once bound to GTP, Rho can then go on to activate various proteins responsible for cytoskeleton regulation such as Rho-kinase ( ... Action potential Voltage-dependent calcium channel Calcium-activated potassium channel Cyclic nucleotide-gated ion channel Acid ... The primary effectors of Gβγ are various ion channels, such as G-protein-regulated inwardly rectifying K+ channels (GIRKs), P/Q ... along the plasma membrane where it may activate any membrane localized forms of a second ser/thr kinase called protein kinase C ...
This activates adenylyl cyclase, which catalyses the conversion of ATP to cyclic AMP (cAMP). cAMP activates protein kinase A, ... UCP1 is very similar to the ATP/ADP Carrier protein, or Adenine Nucleotide Translocator (ANT). The proposed alternating access ... UCP2 localizes to a wide variety of tissues, and is thought to be involved in regulating reactive oxygen species (ROS). In the ... the protein closes the cytoplasmic side so the substrate is enclosed in the protein, and then the matrix side of the protein ...
CNG channel activity is controlled by the interaction between cGMP-dependent protein kinase and G1 protein because of cGMP's ... Like mammalian CNG channels, binding of cyclic nucleotides to the CNBDs has been shown to regulate channel activity and alter ... Cyclic nucleotide gated channel alpha-subunits include Cyclic nucleotide-gated channel alpha 1 Cyclic nucleotide-gated channel ... alpha 2 Cyclic nucleotide-gated channel alpha 3 Cyclic nucleotide-gated channel alpha 4 Cyclic nucleotide gated channel beta- ...
2001). "T cell activation up-regulates cyclic nucleotide phosphodiesterases 8A1 and 7A3". Proc. Natl. Acad. Sci. U.S.A. 98 (11 ... Tat protein down-regulates CREB transcription factor expression in PC12 neuronal cells through a phosphatidylinositol 3-kinase/ ... 2003). "Comparison of enzymatic characterization and gene organization of cyclic nucleotide phosphodiesterase 8 family in ... High affinity cAMP-specific and IBMX-insensitive 3',5'-cyclic phosphodiesterase 8A is an enzyme that in humans is encoded by ...
In mammals, microRNAs (miRNAs) regulate about 60% of the transcriptional activity of protein-encoding genes.[36] Some miRNAs ... nucleotide binding. • DNA binding. • DNA-dependent ATPase activity. • recombinase activity. • chromatin binding. • DNA ... response to organic cyclic compound. • regulation of double-strand break repair via homologous recombination. • DNA metabolic ... Lin HR, Ting NS, Qin J, Lee WH (Sep 2003). "M phase-specific phosphorylation of BRCA2 by Polo-like kinase 1 correlates with the ...
"Tonicity-responsive enhancer binding protein regulates the expression of aldose reductase and protein kinase C δ in a mouse ... "Decreased expression of cyclic adenosine monophosphate-regulated aldose reductase (AKR1B1) is associated with malignancy in ... The way it binds NADPH differs from other nucleotide adenine dinucleotide-dependent enzymes. The active site pocket of human ... stress-activated protein kinase signaling cascade. • cellular response to peptide. • daunorubicin metabolic process. • ...
... regulate G proteins in several different ways. Small GTPases act as molecular switches in ... are activated by a class of proteins called Guanosine nucleotide exchange factors (GEFs). GEFs catalyse nucleotide exchange by ... 3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... Another class of regulatory proteins, the Guanosine nucleotide dissociation inhibitors (GDIs), bind to the GDP-bound form of ...
response to organic cyclic compound. • negative regulation of cyclin-dependent protein serine/threonine kinase activity. • ... "Human CUL-1 associates with the SKP1/SKP2 complex and regulates p21CIP1/WAF1 and cyclin D proteins". Proceedings of the ... but not PCNA dependent nucleotide excision repair (NER).[21] As such, p21 acts as an effective inhibitor of DNA S-phase DNA ... cyclin-dependent protein serine/threonine kinase activity. • protein kinase inhibitor activity. • protein kinase binding. • ...
protein binding. • hydrolase activity. • protein kinase binding. • serine hydrolase activity. Cellular component. • cytoplasm. ... 2002). "Stimulation of lipolysis and hormone-sensitive lipase via the extracellular signal-regulated kinase pathway". J. Biol. ... which is necessary for lipid mobilization in response to cyclic AMP, which itself is provided by the activation of Gs protein- ... Also, it may be activated by a cAMP-dependent protein kinase (PKA). This pathway is significantly less effective than the first ...
Guanine nucleotide-binding protein G(I)/G(S)/G(T) subunit beta-1 is a protein that in humans is encoded by the GNB1 gene.[5] ... 1omw: Crystal Structure of the complex between G Protein-Coupled Receptor Kinase 2 and Heterotrimeric G Protein beta 1 and ... 1b9y: STRUCTURAL ANALYSIS OF PHOSDUCIN AND ITS PHOSPHORYLATION-REGULATED INTERACTION WITH TRANSDUCIN BETA-GAMMA ... protein complex binding. • signal transducer activity. • protein binding. • GTPase activity. • GTPase binding. • G-protein ...
G proteins, also known as guanine nucleotide-binding proteins, are a family of proteins that act as molecular switches inside ... G proteins regulate metabolic enzymes, ion channels, transporter proteins, and other parts of the cell machinery, controlling ... 3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... Types of G protein signaling[edit]. G protein can refer to two distinct families of proteins. Heterotrimeric G proteins, ...
G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger. ... receptor channels through activation of anchored protein kinase C in prefrontal cortical neurons". The Journal of Neuroscience ... 5-HT2A serotonin receptor antagonists differentially regulate 5-HT2A receptor protein level in vivo". The Journal of ... G-protein coupled receptor activity. • virus receptor activity. • signal transducer activity. • drug binding. • G-protein alpha ...
Phosphorylation by cAMP-dependent protein kinasesEdit. Cyclic AMP-dependent protein kinases (protein kinase A) are activated by ... Protein kinase A is an important enzyme in cell metabolism due to its ability to regulate cell metabolism by phosphorylating ... proteins such as GEFs, guanine-nucleotide dissociation inhibitors (GDIs) and protein phosphatases. There may even be specific ... The G protein-coupled receptor kinases (GRKs) are protein kinases that phosphorylate only active GPCRs.[53] G-protein-coupled ...
For example, miR-27a up-regulates P-gp expression by suppressing Raf kinase inhibitor protein (RKIP);[27] alternatively, miR- ... nucleotide binding. • transporter activity. • ATPase activity. • protein binding. • hydrolase activity. • ATP binding. • ... Additional structures (3G60 and 3G61) of P-gp were also solved revealing the binding site(s) of two different cyclic peptide ... Mitogen-activated protein kinase (MAPK) signaling pathways includes three pathways: the classical MAPK/ERK pathway, p38 MAPK ...
Phosphorylation of a protein by a kinase can activate a cascade such as the mitogen-activated protein kinase cascade.[23] ... A second magnesium ion is critical for ATP binding in the kinase domain.[6] The presence of Mg2+ regulates kinase activity.[7] ... The amino acid is coupled to the penultimate nucleotide at the 3′-end of the tRNA (the A in the sequence CCA) via an ester bond ... cyclic AMP, which is involved in triggering calcium signals by the release of calcium from intracellular stores.[24] This form ...
3',5'-cyclic-GMP phosphodiesterase. *Protein kinase G. *G alpha subunit Gα *GNAO1 ... Because RETGC-1 produces cGMP, which keeps cyclic nucleotide-gated channels open allowing the influx of calcium, this mutation ... Calcium, which plays many roles in the cell and is tightly regulated, disrupts the membrane when it appears in excess. Also, ... Guanylyl cyclase activator (protein). References[edit]. *^ Sakurai K.; Chen J.; Kefalov V. (2011). "Role of guanylate cylcase ...
... that phosphorylate and thereby regulate target proteins involved in cell signaling (see Protein kinase C#Function). Studies ... G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger. • response to lipopolysaccharide. ... protein kinase Cs, calmodulin-modulated myosin light chain kinase, RAF/MEK/Mitogen-activated protein kinases, PKC/Ca2+/ ... "Protein kinase A-mediated phosphorylation of serine 357 of the mouse prostacyclin receptor regulates its coupling to G(s)-, to ...
cellular response to organic cyclic compound. • natural killer cell activation. • negative regulation of I-kappaB kinase/NF- ... protein complex binding. • scaffold protein binding. • protein binding. • identical protein binding. • cysteine-type ... nucleotide-binding oligomerization domain containing signaling pathway. • T cell activation. • suppression by virus of host ... a novel FADD-like anti-apoptotic molecule that regulates Fas/TNFR1-induced apoptosis". J. Biol. Chem. 272 (30): 18542-5. doi: ...
... coupled to cyclic nucleotide second messenger. • chemotaxis. • positive regulation of G-protein coupled receptor protein ... DAG activates certain protein kinase C enzymes )PKCs) that phosphorylate and thereby regulate target proteins involved in cell ... signaling; and adenyl cyclase converts AMP into cyclic AMP (cAMP) thereby down-regulating cAMP-responsive proteins involved in ... G-protein coupled receptor signaling pathway. • adenylate cyclase-inhibiting G-protein coupled receptor signaling pathway. • G- ...
Yeast tRNA kinase then phosphorylates the 5'-hydroxyl group using adenosine triphosphate. Yeast tRNA cyclic phosphodiesterase ... alternative splicing of pre-mRNA transcripts is regulated by a system of trans-acting proteins (activators and repressors) that ... exon then performs a nucleophilic attack at the first nucleotide following the last nucleotide of the intron at the 3' splice ... Protein splicing[edit]. Main article: Protein splicing. In addition to RNA, proteins can undergo splicing. Although the ...
G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger. • response to nicotine. • aging. • ... which are activated by cAMP-dependent interaction with such molecules as protein kinase A (PKA), protein kinase C (PKC), Raf-1 ... mGlu5 forms a heterodimer with A2A, which allows endocannabinoids to regulate their own levels, as they inhibit cAMP production ... and increases mitogen-activated protein kinase (MAP kinase) concentration. Alternatively, in some rare cases CB1 receptor ...
... nuclear located protein kinase C and cyclic AMP-dependent protein kinase". Frontiers in Bioscience. 13 (13): 1206-26. doi: ... a sphingolipid derived from ceramide that is a potent messenger molecule involved in regulating calcium mobilization,[74] cell ... involved in calcium-mediated activation of protein kinase C;[76] the prostaglandins, which are one type of fatty-acid derived ... Protein-lipid interaction. *Phenolic lipid, a class of natural products composed of long aliphatic chains and phenolic rings ...
cAMP, which is the second messenger here, opens a cyclic nucleotide-gated ion channel (CNG), producing an influx of cations ( ... in that cAMP works by directly binding to the ion channel rather than through activation of protein kinase A. It is similar to ... For example, the Bay Area Air Quality Management District has applied its standard in regulating numerous industries, landfills ... A modern demonstration of that theory was the cloning of olfactory receptor proteins by Linda B. Buck and Richard Axel (who ...
... signaling via guanine nucleotide-binding proteins (G proteins) and downstream effectors such as adenylate cyclase. The CRF2 ... regulation by glucocorticoids and the cyclic adenosine 5'-monophosphate pathway". Endocrinology. 145 (12): 5605-15. doi:10.1210 ... "Urocortin II is expressed in human pregnant myometrial cells and regulates myosin light chain phosphorylation: potential role ... G-protein coupled receptor activity. • signal transducer activity. • protein binding. • corticotrophin-releasing factor ...
HIPK2 is a protein that regulates Mdm2 in this way. The induction of the p14arf protein, the alternate reading frame product of ... protein domain specific binding. • receptor serine/threonine kinase binding. • peroxisome proliferator activated receptor ... cellular response to organic cyclic compound. • viral process. • response to iron ion. • regulation of gene expression. • ... of Mdm2 is unique in that it incorporates a conserved Walker A or P-loop motif characteristic of nucleotide binding proteins, ...
G protein-coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger. • multicellular organism ... positive regulation of protein kinase B signaling. • positive regulation of protein kinase C signaling. • G protein-coupled ... MC1R is one of the key proteins involved in regulating mammalian skin and hair color. It is located on the plasma membrane of ... positive regulation of protein kinase A signaling. • GO:0007243 intracellular signal transduction. • pigmentation. • positive ...
Bellamacina CR (1 September 1996). "The nicotinamide dinucleotide binding motif: a comparison of nucleotide binding proteins". ... emerges as an adenine nucleotide that can be released from cells spontaneously and by regulated mechanisms,[35][36] and can ... In a further step, some NAD+ is converted into NADP+ by NAD+ kinase, which phosphorylates NAD+.[23] In most organisms, this ... Lee HC (2002). Cyclic ADP-Ribose and NAADP: Structure, Metabolism and Functions. Kluwer Academic Publishers. ISBN 1-4020-7281-3 ...
... "a step along the path toward amino acids and nucleotides, the raw materials of proteins and DNA, respectively".[108][109] ... and also affect mitogen-activated protein kinases that activate transcription factors involved in cell proliferation.[83] ... When the DNA sequence is altered in genes that regulate cell replication, cancer can result. Mutagenic PAHs, such as benzo[a] ... In theory, there are 51 structural isomers of coronene that have six fused benzene rings in a cyclic sequence, with two edge ...
Protein kinases can also be inhibited by competition at the binding sites where the kinases interact with their substrate ... This block of nucleotide biosynthesis is more toxic to rapidly growing cells than non-dividing cells, since a rapidly growing ... However, metabolic pathways are not just regulated through inhibition since enzyme activation is equally important. With ... the enzyme that degrades the signalling molecule cyclic guanosine monophosphate.[40] This signalling molecule triggers smooth ...
A C-terminal region of the CagA protein (amino acids 873-1002) has also been suggested to be able to regulate host cell gene ... the CagA protein is phosphorylated on tyrosine residues by a host cell membrane-associated tyrosine kinase (TK). CagA then ... While cyclic AMP and butyrate synergistically stimulate the expression of chicken β-defensin 9 [297], 4-phenylbutyrate (PBA) ... presented a comprehensive analysis of transcription at single-nucleotide resolution by differential RNA-seq that confirmed the ...
G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger. • protein import into nucleus, ... protein binding. • receptor serine/threonine kinase binding. Cellular component. • cytoplasm. • axon terminus. • integral ... The human delta -opioid receptor displays constitutive oligomerization at the cell surface, which is not regulated by receptor ... Guo J, Wu Y, Zhang W, Zhao J, Devi LA, Pei G, Ma L (Nov 2000). "Identification of G protein-coupled receptor kinase 2 ...
G-protein coupled receptor signaling pathway, coupled to cyclic nucleotide second messenger. • negative regulation of action ... Involvement of both mitogen-activated protein kinase and induction of Krox-24 expression". European Journal of Biochemistry / ... which critically regulates a number of important cellular processes in both mature and developing tissues.[16] Activation of ... "Regulation of cell motility by mitogen-activated protein kinase". The Journal of Cell Biology. 137 (2): 481-92. doi:10.1083/jcb ...
... kinase. In this pathway, recruitment of a guanine nucleotide exchange factor by the adaptor and docking proteins leads to ... act to phosphorylate the cyclic AMP response element binding protein (CREB) transcription factor.[7] Phosphorylated CREB ... The activated transcription factor c-Jun regulates nuclear transcription via AP-1 to increase pro-apoptotic gene transcription. ... The active Ras protein phosphorylates several proteins, along with the serine/threonine kinase, Raf.[7] Raf in turn activates ...
Cyclic Nucleotide-Regulated Protein Kinases*Cyclic Nucleotide-Regulated Protein Kinases. *Cyclic Nucleotide Regulated Protein ... "Cyclic Nucleotide-Regulated Protein Kinases" by people in this website by year, and whether "Cyclic Nucleotide-Regulated ... Protein-Serine-Threonine Kinases [D08.811.913.696.620.682.700]. *Cyclic Nucleotide-Regulated Protein Kinases [D08.811.913.696. ... "Cyclic Nucleotide-Regulated Protein Kinases".. *Cyclic Nucleotide-Regulated Protein Kinases. *Cyclic AMP-Dependent Protein ...
Epac is a cyclic adenosine 5-monophosphate-activated guanine nucleotide exchange factor for Rap1. In this study, we show that ... A novel interplay between Epac/Rap1 and mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5 ... A novel interplay between Epac/Rap1 and mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5 ... A novel interplay between Epac/Rap1 and mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5 ...
Determination of cyclic nucleotide-dependent protein kinase substrate specificity by the use of peptide libraries on cellulose ... Activation of mitogen-activated protein kinase pathways by cyclic GMP and cyclic GMP-dependent protein kinase in contractile ... we identified cyclic GMP (cGMP)-dependent protein kinases (PKGs) regulated by nitric oxide (NO) signaling to be novel K-Ras ... Nitric Oxide Synthase Signaling Regulates K-Ras Plasma Membrane Interactions via Cyclic GMP-Dependent Protein Kinase 2. Kwang- ...
"Protein phosphorylation regulated by cyclic nucleotide-dependent protein kinases in cell extracts and in intact human ... VASP is regulated by the cyclic nucleotide-dependent kinases PKA and PKG. Vasodilator-stimulated phosphoprotein has been shown ... "The vasodilator-stimulated phosphoprotein is regulated by cyclic GMP-dependent protein kinase during neutrophil spreading". J. ... 2000). "Fyn-binding protein (Fyb)/SLP-76-associated protein (SLAP), Ena/vasodilator-stimulated phosphoprotein (VASP) proteins ...
2004) Roles of Ca2+, hyperpolarization and cyclic nucleotide-activated channel activation, and actin in temporal synaptic ... 2002) Participation of protein kinase C alpha isoform and extracellular signal-regulated kinase in neurite outgrowth of GT1 ... blockers of ERK1/2 kinase [i.e., mitogen-activated protein kinase kinase (MEK)], were dissolved in 50% dimethylsulfoxide (DMSO ... Phosphorylated extracellular signal-regulated protein kinase 1/2 (pERK1/2) and actin cytoskeleton are strong candidates for ...
Cyclic Nucleotide-Gated Channels Martin Biel, Stylianos Michalakis. Pages 111-136 * cGMP Regulated Protein Kinases (cGK) ... A Short History of cGMP, Guanylyl Cyclases, and cGMP-Dependent Protein Kinases ... This book is an enthusiastic celebration of cyclic guanosine monophosphate (cGMP) and amply illustrates the importance of this ...
"Protein kinase A-dependent cooperation between GATA and CCAAT/enhancer-binding protein transcription factors regulates ... The cyclic nucleotides and protein kinases may play an important role in the pathophysiology of testicular infarction in SCD. ... Sickling Cells, Cyclic Nucleotides, and Protein Kinases: The Pathophysiology of Urogenital Disorders in Sickle Cell Anemia. ... DSM physiology also involves cyclic nucleotides and activation of protein kinases. DSM contractions are a consequence of ...
Regulate: ion channels protein kinases. phosphatases cyclic nucleotide phosphodiesterases Decks in Molecules to Medicine III ... Protein Kinase C (PKC). - translocate to membrane. Synaptotagmin - Ca2+ dependent fusion of synaptic vesicles. Calmodulin. - ...
While protein kinase A (PKA) or cAMP-dependent protein kinase and cyclic nucleotide regulated ion channel (CNG and HCN) were ... opposing effects of exchange protein directly activated by cyclic AMP and cAMP-dependent protein kinase on protein kinase B ... or cAMP-regulated guanine nucleotide exchange factor I (cAMP-GEFI) is a protein that in humans is encoded by the RAPGEF3 gene. ... "The protein kinase A anchoring protein mAKAP coordinates two integrated cAMP effector pathways". Nature. 437 (7058): 574-8. doi ...
... that the absence of PDE1B2 activity may affect localized pools of cyclic nucleotide that can regulate different protein kinase ... PDE1B2 Regulates Cyclic Nucleotide Levels in Differentiated HL-60 Cells. Monocytes and macrophages respond to a variety of ... Cyclic nucleotide phosphodiesterases (PDEs) are enzymes that regulate the amplitude and duration of cAMP and cGMP signaling by ... The concept that PDE1B2 could regulate a specific localized cyclic nucleotide pool is supported by the observation that the ...
The budding of HIV from infected cells is driven by the protein-protein interaction between the p6 domain of the HIV Gag ... protein and the UEV domain of the human... ... thereby activates CYCLIC NUCLEOTIDE-REGULATED PROTEIN KINASES. ... The binding of calcium ions to this protein allows this protein to bind to cyclic nucleotide phosphodiesterases and to adenyl ... Design of Cyclic Peptides as Protein Recognition Motifs.. Protein-protein interactions are ubiquitous, essential to almost all ...
... and cGMP-regulated enzymes like cGMP-dependent protein kinase and cyclic nucleotide gated channels are described. Anatomical ...
The existence of eukaryotic CNB domains not associated with binding of cyclic nucleotides suggests that orphan CNB domains in ... Protein kinase A (PKA) is typically activated by cAMP. Here, Bachmaier et al. show that PKA of Trypanosoma is activated by ... Protein kinase A (PKA), the main effector of cAMP in eukaryotes, is a paradigm for the mechanisms of ligand-dependent and ... Shalaby, T., Liniger, M. & Seebeck, T. The regulatory subunit of a cGMP-regulated protein kinase A of Trypanosoma brucei. Eur. ...
Epac is also able to activate extracellular signal-regulated protein kinases (ERK, a mitogen-activated protein kinase) through ... exchange proteins directly activated by cyclic AMP. Epac1 and 2 are guanine nucleotide exchange factors for members of the Ras ... THOMAS, R, WOON, ML, RALEVIC, V and ALEXANDER, SPH, An investigation of the role of cyclic nucleotides and potassium channels ... WALLACE, KE, HERNANDEZ, F, KENDALL, DA and ALEXANDER, SPH, THE EFFECTS OF ISOPRENALINE ON CYCLIC-NUCLEOTIDE LEVELS IN THE ...
Egress is absolutely dependent upon the activity of a parasite cGMP-dependent protein kinase, PKG, and so is influenced by ... levels of intracellular cGMP (Collins et al., 2013). This is regulated by the interplay between guanylate cyclases and ... The merozoites invade fresh red blood cells, a process that involves shedding of a microneme protein called apical membrane ... to capture and immobilize the protein from culture supernatants, then uses a specific rabbit polyclonal antiserum to detect the ...
... on WN Network delivers the latest Videos and Editable pages for News & Events, including ... VASP is regulated by the cyclic nucleotide-dependent kinases PKA and PKG. ... Ena/Vasp homology proteins. ENA/VASP Homology proteins or EVH proteins are a family of closely related proteins involved in ... EVH proteins are modular proteins that are involved in actin polymerization, as well as interaction with other proteins. Within ...
... cAMP activates protein kinase A (PKA), which can regulate other intracellular events, including transcription of cAMP-regulated ... leading to the production of cyclic AMP (cAMP) from ATP. cAMP gates or opens the cyclic nucleotide-gated (CNG) ion channel, ... General anosmia caused by a targeted disruption of the mouse olfactory cyclic nucleotide-gated cation channel. Neuron. 17:681- ... The increase in intracellular cAMP "gates" or opens a cyclic nucleotide-gated (CNG) channel, leading to an influx of sodium and ...
... signalling regulates multiple biological functions through activation of protein kinase G and cyclic nucleotide-gated (CNG) ... PTEN induced kinase 1 (PINK1) is a serine/threonine kinase in the outer membrane of mitochondria (OMM), and known as a ... The pro-apoptotic Bcl-2-family protein Bim belongs to the BH3-only proteins known as initiators of apoptosis. Recent data show ... It is possible that the secondary structure of β-barrel proteins plays a role in directing these proteins to mitochondria. ...
... signalling regulates multiple biological functions through activation of protein kinase G and cyclic nucleotide-gated (CNG) ... specific channels by fusing a bacterial photoactivated adenylyl cyclase to cyclic nucleotide-gated channels with high ... Optogenetic manipulation of cGMP in cells and animals by the tightly light-regulated guanylyl-cyclase opsin CyclOp (2015) ... Overexpression of Vc2c-Cyclop1 protein in V. carteri led to a significant increase of cGMP, demonstrating enzyme functionality ...
... including cyclic-nucleotide and calcium-phospholipid-dependent kinases, ribosomal S6-phosphorylating kinases, G protein-coupled ... kinases and all close relatives of these sets); the CAMKs (calmodulin-regulated kinases); the CK1 group (casein kinase 1, and ... 4. Hanks SK, Hunter T. Protein kinases 6. The eukaryotic protein kinase superfamily: kinase (catalytic) domain structure and ... The Protein Kinase Resource (68) collates data from several databases and includes a subset of protein kinase 3D structures to ...
Potent selective inhibitor of protein kinase G I a, I ß and especially of type II. Activates retinal cGMP channels and thus ... "The Vasodilator-stimulated Phosphoprotein is Regulated by Cyclic GMP-dependent Protein Kinase During Neutrophil Spreading" ... 12th Protein Kinase Symp. NO/cGMP and Protein Kinase Signaling Bad Brückenau/Germany, 0, 0 - 0 (2000), "Protein Kinase A Type I ... Sci., 36, 275 - 328 (1999), "Cyclic Nucleotide-Dependent Protein Kinases: Intracellular Receptors for cAMP and cGMP Action" ...
Mitogen-Activated Protein Kinase 3 * p38 Mitogen-Activated Protein Kinases * Cyclic Nucleotide Phosphodiesterases, Type 4 ... extracellular signal-regulated kinase, Akt/mammalian target of rapamycin kinase, and nuclear factor-kappa B Nutr Cancer. 2014; ... whereas it attenuates p44/42 extracellular signal-regulated kinase activity and the Akt/mammalian target of rapamycin kinase ... intracellular cAMP levels and increases the activity of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, ...
2013 The C. elegans cGMP-dependent protein kinase EGL-4 regulates nociceptive behavioral sensitivity. PLoS Genet. 9: e1003619. ... 2007 Biochemistry and physiology of cyclic nucleotide phosphodiesterases: essential components in cyclic nucleotide signaling. ... they can be regulated by cGMP, cAMP, calcium, kinases, and the γ subunit of heteromeric G proteins (Conti and Beavo 2007; ... including cyclic nucleotide-gated channels and kinases, can act rapidly by changing the membrane potential of a cell (e.g., the ...
... that is subsequently generated by sGC regulates the activity of cGMP-dependent protein kinases such as protein kinase G (PKG), ... C. L. Miller, Y. Cai, M. Oikawa et al., "Cyclic nucleotide phosphodiesterase 1A: a key regulator of cardiac fibroblast ... such as mitogen-activated protein kinases (MAPKs) and protein kinase C (PKC). TGFβ signal transducers subsequently activate the ... protein tyrosine phosphatases (PTPs), and protein tyrosine kinases via reversible oxidation of thiol groups of low pKa cysteine ...
Identification and classification of CNB domains in Global Ocean Sampling and other protein sequences reveals that they ... domain regulates signaling pathways in both eukaryotes and prokaryotes. In this study, we analyze the evolutionary information ... the protein kinase A (PKA) regulatory subunit that regulates the activity of PKA [3, 4]; the guanine nucleotide exchange factor ... The cyclic nucleotide binding (CNB) domain regulates signaling pathways in both eukaryotes and prokaryotes. In this study, we ...
... protein kinase A (PKA), exchange proteins regulated by cAMP (EPAC) and cyclic nucleotide gated ion-channels. The sole mechanism ... It functions as an adaptor protein in the c-Raf/MEK/ERK cascade by interacting with c-Raf and ERK.. In this study, I have shown ... SUMOylation of proteins is an important method of regulation. In the current study, preliminary investigations were undertaken ... β-arrestin interacts with PDE4D5 and is a multifunctional protein that plays pivotal roles in signal transduction. ...
... proteolipid protein (PLP), myelin basic protein (MBP), 2′, 3′-cyclic nucleotide 3′-phosphohydrolase (CNPase), MAG, and several ... a brain-derived DNA-binding protein with a capacity to regulate expression of myelin basic protein gene. J Biol Chem 269:31149- ... 1992) Phosphorylation of CCAAT-enhancer binding protein by protein kinase C attenuates site-selective DNA binding. J Biol Chem ... The protein tyrosine kinase Fyn activates transcription from the HIV promoter via activation of NFκB-like DNA-binding proteins. ...
... and activation of cGMP-dependent protein kinase. This book chapter provides an overview of the progress being made in ... through the increase of the second messenger cyclic guanosine monophosphate (cGMP) ... which culminates with the phosphorylation of the transcription factor cAMP-responsive element-binding protein (CREB) ... cyclic nucleotides play an important role in the regulation of CREB phosphorylation through the activation of cyclic nucleotide ...
... signalling regulates multiple biological functions through activation of protein kinase G and cyclic nucleotide-gated (CNG) ... Thus, we generated a highly efficient blue ChR2, the H134R; T159C double mutant (ChR2-HR/TC). Both proteins can be used in the ... Optogenetic manipulation of cGMP in cells and animals by the tightly light-regulated guanylyl-cyclase opsin CyclOp (2015) ... Optogenetic approaches using light-activated proteins like Channelrhodopsin-2 (ChR2) enable investigating the function of ...
... we found no biochemical or bioinformatic evidence for a plant cyclic nucleotide regulated protein kinase, suggesting that ... With an understanding of the protein domains which can bind cyclic nucleotides (CNB and GAF domains) we scanned the completed ... and resolves a longstanding debate about the presence of a cyclic nucleotide dependent kinase in plants. ... found that several ion channels and a class of thioesterases constitute the possible cyclic nucleotide binding proteins in ...
  • Cyclic nucleotide phosphodiesterases (PDEs) are enzymes that regulate the amplitude and duration of cAMP and cGMP signaling by controlling cyclic nucleotide (cNT) degradation. (
  • 2013). This is regulated by the interplay between guanylate cyclases and phosphodiesterases. (
  • Absolutely resistant against mammalian cyclic nucleotide-dependent phosphodiesterases, no metabolic side effects. (
  • cGMP plays a role in sensory signaling and plasticity by regulating ion channels, phosphodiesterases, and kinases. (
  • Such a reporter can be used to illuminate how producers (guanylyl cyclases) and degraders (phosphodiesterases) of cGMP shape the landscape of this cyclic nucleotide in neurons. (
  • The sole mechanism to inactivate cAMP is through degradation via cyclic-phosphodiesterases (PDEs). (
  • Several other proteins such as cyclic nucleotide gated ion channels ( 1 ), phosphodiesterases (PDE) ( 2 ), and guanine nucleotide exchange factors (Epac) ( 3 ) bind cAMP. (
  • 2,3 Cyclic GMP is degraded by cGMP-hydrolyzing phosphodiesterases (PDEs). (
  • Importantly, pharmacologic and genetic means to increase cellular cAMP levels either by activating cAMP-inducing G-protein-coupled receptors (GPR3 or β 2 adrenergic receptor) or ADCY1, or by inhibiting cAMP-reducing guanine nucleotide-binding protein G(i) subunit α2, C-X-C motif chemokine receptor type 4, or cAMP phosphodiesterases, sensitized cancer cells to CADs. (
  • To locate components and target proteins of relevance for the cAMP and cGMP signaling networks including cAMP and cGMP phosphodiesterases (PDEs), salt-inducible kinases (SIKs), subunits of Na+, K+-ATPases, and aquaporins (AQPs) in the human saccule. (
  • By hydrolyzing cAMP and cGMP, cyclic nucleotide phosphodiesterases (PDEs) regulate a wide variety of biological responses mediated by these second messenger molecules. (
  • GAF domains are ubiquitous motifs present in cyclic GMP (cGMP)‐regulated cyclic nucleotide phosphodiesterases, certain adenylyl cyclases, the bacterial transcription factor FhlA, and hundreds of other signaling and sensory proteins from all three kingdoms of life. (
  • The increase in cGMP concentrations is known to activate different signaling mediators, such as cyclic nucleotide phosphodiesterases, cGMP-regulated ion channels, and cGMP-dependent protein kinases (cGKs). (
  • Cyclic GMP affects the activity of effector molecules, specifically cGMP-dependent protein kinases (PKG), cGMP-regulated phosphodiesterases (PDEs), and cGMP-regulated cation channels. (
  • The physiological effects of natriuretic peptides are elicited through three classes of cGMP binding proteins: cGMP-dependent protein kinases, cGMP-regulated phosphodiesterases, and cyclic nucleotide-gated ion channels. (
  • It is now well established that cyclic nucleotide phosphodiesterases (PDEs) play an important role in the regulation of cAMP signaling in the heart. (
  • Phosphodiesterases (PDEs) are a family of phosphohydrolyases that catalyze the hydrolysis of 3' cyclic phosphate bonds in adenosine and/or guanine 3',5' cyclic monophosphate (cAMP and/or cGMP). (
  • cGMP-driven activation of protein kinases, ion channels, or phosphodiesterases (PDEs) causes a broad variety of physiological responses whereas dysregulation can result in severe pathologies. (
  • A group of enzymes that catalyzes the phosphorylation of serine or threonine residues of proteins and is dependent on cyclic nucleotides. (
  • K-Ras phosphorylation by PKG2 is triggered by activation of AMP-activated protein kinase (AMPK) and requires endothelial nitric oxide synthase and soluble guanylyl cyclase. (
  • Also, PDE1B2 knockdown cells have lower basal levels of cAMP and alterations in the phosphorylation state of several probable PKA substrate proteins. (
  • The regulation of protein function through reversible phosphorylation by protein kinases and phosphatases is a general mechanism controlling virtually every cellular activity. (
  • The regulation of protein function through reversible phosphorylation by protein kinases and phosphatases is a widespread cellular mechanism thought to control virtually every cellular activity ( 1 ), and abnormal levels of phosphorylation are known to be responsible for severe diseases ( 2 ). (
  • 2) Disruption of this association by mutagensis or small peptides decreases the phosphorylation of Ser412 on β-arrestin1, and accelerates isoprenaline-stimulated G-protein coupled receptor (GPCR) internalization. (
  • A vast number of studies have focused on understanding the nitric oxide (NO) signaling pathway, which culminates with the phosphorylation of the transcription factor cAMP-responsive element-binding protein (CREB) through the increase of the second messenger cyclic guanosine monophosphate (cGMP) and activation of cGMP-dependent protein kinase. (
  • We focus here on the content and diversity of protein kinases present in worms, together with an assessment of other classes of proteins that regulate protein phosphorylation. (
  • Finally, the richness of phosphorylation-dependent signaling pathways in worms is further supported with the identification of 185 protein phosphatases and 128 phosphoprotein-binding domains (SH2, PTB, STYX, SBF, 14-3-3, FHA, and WW) in the worm genome. (
  • Reversible protein phosphorylation plays a central role in regulating basic functions of all eukaryotes such as DNA replication, cell cycle control, gene transcription, protein translation, and energy metabolism. (
  • Protein phosphorylation is also required for more advanced functions in higher eukaryotes such as cell, organ, and limb differentiation, cell survival, synaptic transmission, cell-substratum and cell-cell communication, and to mediate complex interactions with the external environment. (
  • Because aberrant protein phosphorylation is commonly the cause of cancer and other human diseases, a comprehensive knowledge of the key enzymes that regulate these functions can provide the basis for novel therapeutic intervention strategies. (
  • Here, we present a comparative analysis of the enzymes and adaptor molecules that are the key components of the protein phosphorylation signaling network present in C. elegans . (
  • Ca 2+ sensors activate transcription factors (TF) and other proteins either by direct binding or through phosphorylation (P). TFs bind DNA and cause up‐ or down‐regulation of gene expression. (
  • Substantial evidence links increases in intracellular cAMP to activation of cAMP-dependent protein kinase (PKA) and subsequent phosphorylation of downstream effectors (transcription factors, receptors, protein kinases) necessary for long-term potentiation (LTP) of synaptic strength. (
  • The Ca 2+ /calmodulin-dependent kinase kinase/AMP activated protein kinase pathway seems to be greatly involved as STO-609 and Compound C, Ca 2+ /calmodulin protein kinase kinase/AMP kinase inhibitors respectively, cancelled eNOS phosphorylation induced by PHA. (
  • Several kinases regulate eNOS phosphorylation including AMP-activated protein kinase (AMPK) [2-4]. (
  • Benz A, Shajari M, Peruzki N, Dehghani F, Maronde E (2010) A novel mechanism for transient Egr-1 protein induction via FGF-1-induced MAPK phosphorylation and PKB/Akt-dephosphorylation in hippocampal neurons. (
  • To examine these phenomena, we characterized agonist activation of ERK1/2 in HEK293 cells by the endogenous β 2 AR and in HEK293 cells stably overexpressing either the wild-type β 2 AR or a substitution mutant β 2 AR (PKA − ) that lacks the cyclic AMP-dependent protein kinase (PKA) consensus phosphorylation sites (S261A, S262A and S345A, S346A). (
  • The cGMP sensitivity of cyclic nucleotide-gated (CNG) channels can be modulated by changes in phosphorylation catalyzed by protein tyrosine kinases (PTKs) and protein tyrosine phosphatases. (
  • FK stimulated the phosphorylation of extracellular signal-activated kinases (ERK) 1/2 in a subpopulation of dopaminergic neurons, suggesting that the mitogen-activated protein kinase (MAPK) pathway was involved in the effects of cAMP-elevating agents. (
  • Additionally, CBN did not attenuate FITC-triflavin binding or phosphorylation of proteins, such as integrin β 3 , Src, and focal adhesion kinase, in platelets spreading on immobilized fibrinogen. (
  • PDE4B limited the PKA-mediated phosphorylation of key players in excitation-contraction coupling that reside in the sarcolemmal compartment, including L-type Ca 2+ channels and ryanodine receptors, but not phosphorylation of distal cytosolic proteins. (
  • Paxillin has been found to play an important role in cell differentiation, and its phosphorylation is regulated by NO in cultured SMCs. (
  • 6 Tyrosine phosphorylation of paxillin is associated with cytokines, mitogenic peptides, growth factors, and extracellular matrix protein-stimulated signal transduction, including the mitogen-activated protein kinase pathway that is involved in cell migration and proliferation. (
  • cAMP is involved in the activation of protein kinases and regulates the phosphorylation of a variety of substrates. (
  • Treatment with fMLF induced phosphorylation of soluble N -ethylmaleimide-sensitive factor-attachment protein (SNAP)-23, syntaxins 2, 4, and 6, and Monc18-3. (
  • These results suggest that PKG and PI3K are involved in degranulation, possibly through phosphorylation of target membrane SNAP receptor proteins and their binding proteins. (
  • Research conducted thus far has led to the identification of several important regulatory mechanisms for leukocyte degranulation, including elevation of intracellular Ca 2+ concentration, activation of the cytoskeletal contractile apparatus, and phosphorylation of the soluble N -ethylmaleimide-sensitive factor-attachment protein (SNAP) 3 receptor proteins (SNAREs). (
  • Phosphorylation of syntaxins, Munc18, and SNAP-23 is catalyzed by kinases such as protein kinase C (PKC) ( 12 , 13 , 14 ). (
  • In mast cells, a mechanism of degranulation induced by FcεRI cross-linking involves recruitment and activation of the tyrosine kinases Lyn and Syk, phosphorylation of several tyrosine residues in FcεRI, activation of phospholipase Cγ (PLCγ), and generation of the second messengers diacylglycerol and inositol trisphosphate ( 1 , 15 ). (
  • We've also discovered that rhodopsin-regulated Src kinase activation in retina qualified prospects towards the phosphorylation of Grb14. (
  • Although it is assumed that these changes in PDE activity have important consequences in the cell, the function of most of the individual PDEs up-regulated with differentiation has not yet been addressed. (
  • It appears that for such events a supramolecular complex is required that comprises of the appropriate effector system together with signal termination enzymes such as PDEs and phosphatases that are sequestered by scaffolding proteins ( 4 ). (
  • 6 Like NO, cGMP can affect multiple signaling pathways ( Figure 1 A). 1,5,6 To date, three classes of cGMP receptor proteins have been identified: cyclic nucleotide-gated (CNG) cation channels, cGMP-regulated PDEs, which hydrolyze cAMP and/or cGMP, and cGMP-dependent protein kinases (cGKs). (
  • The allosteric cGMP binding sites on these PDEs have been mapped to two homologous repeats in the N‐terminal halves of the proteins. (
  • 3] Cyclic nucleotide PDEs certainly are a category of ubiquitous enzymes, which selectively hydrolyze the 3 cyclic phosphate connection in cAMP and/or guanosine 3,5 cyclic monophosphate (cGMP). (
  • cGMP-PDEs are the effector molecules in G-protein-mediated phototransduction in vertebrate rods and cones. (
  • PDEs regulate the second messengers by controlling their degradation. (
  • cGMP signaling is abrogated by cGMP hydrolysis via PDEs and cGMP export via multidrug resistance proteins (also referred to as ABC transporters). (
  • This book is an enthusiastic celebration of cyclic guanosine monophosphate (cGMP) and amply illustrates the importance of this field of science to patients and the way in which the field has evolved. (
  • THE canonical second messenger molecule cGMP (cyclic guanosine monophosphate) regulates richly diverse functions in an animal's nervous system. (
  • enzymes catalyze the degradation of cyclic adenosine monophosphate (cAMP) or cyclic guanosine monophosphate (cGMP) to the corresponding AMP or GMP. (
  • Cyclic guanosine monophosphate (cGMP) is a cyclic nucleotide derived from guanosine triphosphate (GTP). (
  • It is cGMP (cyclic guanosine monophosphate) that is responsible for determining the amount of blood that flows in and out of the penis. (
  • We have shown that DNA binding to cGAS robustly induced the formation of … The newest cellular communication process recognized to have such broad and basic importance is the nitric oxide-cyclic guanosine monophosphate (cyclic GMP) signaling pathway. (
  • Nitric oxide (NO)-cyclic guanosine monophosphate (cGMP) signaling plays a critical role in physiological homeostatic processes, such as smooth muscle tone in … DNA binding to cGAS induces a conformational change, leading to the formation of a nucleotide binding pocket and reorganization of the catalytic site (Civril et al. (
  • 2014). Cyclic guanosine monophosphate or cGMP helps arteries relax, which could increase blood flow to the penis. (
  • The overall goal of the DRUGSFORD project was to develop compounds (drugs) and delivery systems for the treatment of RD. Dysregulation of cyclic guanosine monophosphate (cGMP) is a pathological hallmark of RD and cGMP-signalling was therefore chosen as the target for the development of new pharmacological approaches to treat RD. (
  • Cyclic adenosine monophosphate (cyclic AMP or cAMP) and cyclic guanosine monophosphate (cyclic GMP or cGMP) are prolific intracellular signaling molecules. (
  • The nitric oxide/cyclic guanosine monophosphate (NO/cGMP) signaling appears to play a key role in inhibiting neuroinflammation and preventing the activation of a proapoptotic pathway, thereby promoting neural cell survival. (
  • Cyclic guanosine monophosphate (cGMP) is a unique second messenger molecule formed in different cell types and tissues. (
  • Right here, we demonstrate that another ubiquitous second messenger, specifically, 3′-5′ cyclic adenosine monophosphate (cAMP), has a central function in regulating cytosolic Ca2+ amounts and microneme secretion during merozoite invasion of crimson bloodstream cells. (
  • These diseases are also characterized by increased production of cyclic adenosine monophosphate (cAMP), the allosteric activator of cAMP-dependent protein kinase A (PKA). (
  • G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptor (GPCR)-mediated increases in the second messenger cyclic adenosine monophosphate (cAMP) activate the mitogen-activated protein kinase (MAPK) extracellular signal-regulated kinase (ERK), and in neuroendocrine cells, this pathway leads to cAMP-dependent neuritogenesis mediated through Rap1 and B-Raf. (
  • Cyclic adenosine monophosphate (cAMP) plays a central role as a second (intracellular) messenger for the transduction of signals regulating cellular metabolism, secretion, and plasticity by hormones and other first messengers that act through plasma membrane receptors ( 1 ). (
  • The cyclic adenosine monophosphate (cAMP) pathway is crucial for the sympathetic regulation of heart function. (
  • Ras proteins on the PM are spatially organized into nanodomains, called nanoclusters, that are required for high-fidelity signal transduction by the Ras/mitogen-activated protein kinase (MAPK) pathway ( 12 - 14 ). (
  • RACK1, another PDE4D5 binding partner, mediates and initiates cell migration in many cell types and affects the activity of the c-Jun NH2-terminal kinase (JNK) signalling pathway, via its interaction with PKC. (
  • First, publicity of extracellular merozoites to a minimal [K+] environment normal of bloodstream plasma qualified prospects to a growth in cytosolic buy 329907-28-0 Ca2+ with a phospholipase C (PLC)-reliant pathway, which causes translocation of microneme protein such as for example 175 kD erythrocyte binding antigen (EBA175) and apical merozoite antigen-1 (PfAMA1) towards the merozoite surface area [5]. (
  • CAD-induced inhibition of lysosomal acid sphingomyelinase is necessary, but not sufficient, for the subsequent lysosomal membrane permeabilization and cell death, while other pathways regulating this cell death pathway are largely unknown. (
  • Since the endothelial nitric oxide synthase (eNOS)/nitric oxide (NO)/soluble guanylyl cyclase/cGMP/cGMP-dependent protein kinase (PKG) pathway is one of the major antiaggregating mechanism present in platelets, we tested the WGA or PHA effect on this pathway. (
  • Thus, the CaMKK/AMPK pathway activated by PHA can regulate platelet activation stimulating the eNOS/NO/cGMP/PKG signalling pathway. (
  • Farnesol inhibits hyphal growth by regulating the cyclic AMP (cAMP) signalling pathway in C. albicans , and CYR1 and PDE2 regulate a pair of enzymes that are directly responsible for cAMP synthesis and degradation. (
  • Chitinase 1 regulates pulmonary fibrosis by modulating TGF-ß/SMAD7 pathway via TGFBRAP1 and FOXO3. (
  • First, exposure of extracellular merozoites to a low [K + ] environment typical of blood plasma leads to a rise in cytosolic Ca 2+ via a phospholipase C (PLC)-dependent pathway, which triggers translocation of microneme proteins such as 175 kD erythrocyte binding antigen (EBA175) and apical merozoite antigen-1 (PfAMA1) to the merozoite surface [5] . (
  • Due to important roles of cAMP in development of lower eukaryotes and the high conservation of the respective signalling pathway, the main effector of cAMP, protein kinase A (PKA) came into focus. (
  • Although a large number of mammalian RGS proteins are expressed in the heart, 11-13 their specific roles as regulators of parasympathetic pathway effectors are not well understood. (
  • In parallel, activation of EPACs (exchange proteins directly activated by cAMP) causes branching of the cAMP signaling pathway to regulate additional components, most notably the Ca 2+ /calmodulin-dependent protein kinase II ( Grimm and Brown, 2010 ). (
  • The up-regulated gene annotation showed regulation of phospholipase activities, alanine transport, transmembrane receptor protein tyrosine kinase signalling pathway, regulation of blood vessels diameter and 3, 5-cyclic nucleotide phosphodiesterase activity as the five most enriched GO terms. (
  • We propose that the deregulation of the PI3K/PDE3B pathway might result in increased intracellular cyclic AMP accumulation, which promotes apoptosis. (
  • In addition, evidence indicates that cGMP/protein kinase G (PKG) pathway is involved in the modulation of glial cell activity. (
  • cAMP binds Xepac protein enabling it to activate the Ca2 (Montrer CA2 Anticorps )+ pathway, which is necessary to start and maintain X. laevis vitellogenin (Montrer VTG Anticorps ) uptake. (
  • A high manifestation of Grb14 in myocardial cells activates the phosphoinositide 3-kinase (PI3K)-Akt pathway and ablation of Grb14 led to myocardial infarction and reduced PI3K/Akt activation (28). (
  • My central area of research concerns the pharmacology and biochemistry of G protein-coupled receptors (in particular, cannabinoid, adenosine and glutamate) in the CNS and peripheral tissues. (
  • To meet this task, the system utilizes a large family of G protein-coupled receptors-the odorant receptors-which are the chemical sensors underlying the perception of smell. (
  • A large multigene family of olfactory-specific G protein-coupled receptors (GPCRs) was initially identified in the rat ( Buck and Axel, 1991 ) and belongs to what is now referred to as the OR family of odorant receptors ( Mombaerts, 2004 ). (
  • In vitro import assays performed on tryptically digested yeast mitochondria showed reduced Bim insertion into the outer mitochondrial membrane (OMM) indicating that protein receptors may be involved in the import process. (
  • Lots of the essential parasite protein that bind web host receptors are localized in apical organelles known as micronemes. (
  • Invasion of erythrocytes by merozoites can be a complicated multi-step procedure that's mediated by particular molecular relationships between reddish colored cell surface area receptors and parasite proteins ligands [1], [2]. (
  • Subsequently, binding of EBA175 and its own homologs with their erythrocyte receptors causes secretion of rhoptry protein such as for example PfRH2b, Clag3.1 and PfTRAMP [5], [6]. (
  • The three most frequently occurring protein domains found in worms are seven transmembrane chemoreceptors (650 domains, 3.5% of genome), protein kinases (496 domains, 2.6% of genome), and zinc finger C4 domains, including nuclear hormone receptors (275 domains, 1.4% of genome). (
  • The AGC kinase group consists of 63 kinases including the cyclic nucleotide-regulated protein kinase (PKA PKG) family, the diacylglycerol-activated/phospholipid-dependent protein kinase C (PKC) family, the related to PKA and PKC (RAC/Akt) protein kinase family, the kinases that phosphorylate G protein-coupled receptors family (ARK), and the kinases that phosphorylate ribosomal protein S6 family (RSK). (
  • Receptors coupled to heterotrimeric GTP-binding proteins (G-proteins) are integral transmembrane proteins that transduce extracellular signals to the cell interior. (
  • G-protein-coupled receptors exhibit a common structural motif consisting of seven membrane spanning regions. (
  • Structural features of heterotrimeric G-protein-coupled receptors and their modulatory proteins. (
  • Included here are peptides and proteins that regulate the activity of TRANSCRIPTION FACTORS and cellular processes in response to signals from CELL SURFACE RECEPTORS. (
  • The structural and binding studies taken together show that the cGMP binding GAF domains form a new class of cyclic nucleotide receptors distinct from the regulatory domains of cyclic nucleotide‐regulated protein kinases and ion channels. (
  • Alpha 2 adrenergic receptors play an important role in regulating the neuronal release of norepinephrine through presynaptic feedback inhibition in the locus ceruleus. (
  • Many of the key parasite proteins that bind host receptors are localized in apical organelles called micronemes. (
  • Invasion of erythrocytes by P. falciparum merozoites is a complex multi-step process that is mediated by specific molecular interactions between red cell surface receptors and parasite protein ligands [1] , [2] . (
  • Subsequently, binding of EBA175 and its homologs to their erythrocyte receptors triggers secretion of rhoptry proteins such as PfRH2b, Clag3.1 and PfTRAMP [5] , [6] . (
  • G protein (heterotrimeric guanine nucleotide-binding protein)-coupled receptors (GPCRs) are the best candidates for stimulating an increase in cAMP concentration in cells of the nervous system that could, in turn, control ERK activation. (
  • Sympathetic neurotransmitters work via G s -coupled β-adrenergic receptors to increase adenylyl cyclase activity, intracellular cAMP concentration and protein kinase A activity. (
  • cAMP is one of the most common and universal second messengers, and its formation is promoted by adenylyl cyclase (AC) activation after ligation of G protein-coupled receptors (GPCRs) by ligands including hormones, neurotransmitters, and other signaling molecules. (
  • Most neurotransmitter receptors can be divided into two classes by their signal transduction mechanism-one class involving activation of an ion channel that is intrinsic to the receptor and the other involving activation of G proteins. (
  • Many critical drugs that act on the nervous system are agonists or antagonists at G protein-coupled receptors. (
  • Neurotrophins, such as nerve growth factor and brain-derived neurotrophic factor, interact with a family of receptors termed receptor tyrosine kinases (Trks). (
  • Certain cytokines act on receptors that activate Janus kinases, which in turn activate a family of transcription factors called signal transducers and activators of transcription (STATs). (
  • AC is activated by a range of signaling molecules through the activation of AC stimulatory G (G s )-protein-coupled receptors, and inhibited by agonists of AC inhibitory G (G i )-protein-coupled receptors. (
  • Transcripts linked to G protein-coupled receptors and to nitric oxide synthesis were differentially expressed suggesting involvement of these signalling transduction pathways in the response. (
  • Signal transduction via G protein-coupled receptors (GPCRs) was hypothesised in A. fundyense when exposed to the heterotrophic dinoflagellate, but DNA methylation and thus epigenetic regulation was also indicated. (
  • Regulation of these processes by cAMP and cGMP are accompanied by activation of protein kinase A (PKA) and protein kinase G (PKG) , which in turn phosphorylate a variety of substrates, including transcription factors, ion channels and receptors that regulate a variety of physiological processes. (
  • A novel interplay between Epac/Rap1 and mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) regulates thr. (
  • A novel interplay between Epac/Rap1 and mitogen-activated protein kinase kinase 5/extracellular signal-regulated kinase 5 (MEK5/ERK5) regulates thrombospondin to control angiogenesis. (
  • Epac is a cyclic adenosine 5'-monophosphate-activated guanine nucleotide exchange factor for Rap1. (
  • Epac/Rap1 activation down-regulates inhibitor of differentiation 1 (Id1), which negatively regulates thrombospondin-1 (TSP1), an inhibitor of angiogenesis. (
  • Mitogen-activated protein kinase kinase 5, a downstream mediator of vascular endothelial growth factor, antagonizes the effects of Epac/Rap1 by inducing Id1 and suppressing TSP1 expression. (
  • As the name suggests, EPAC proteins (EPAC1 and EPAC2) are a family of intracellular sensors for cAMP, and function as nucleotide exchange factors for the Rap subfamily of RAS-like small GTPases. (
  • This is due to the fact that the net physiological effects of cAMP entail the integration of EPAC- and PKA-dependent pathways, which may act independently, converge synergistically, or oppose each other in regulating a specific cellular function. (
  • In mammals, the EPAC protein family contains two members: EPAC1 (this protein) and EPAC2 (RAPGEF4). (
  • They further belong to a more extended family of Rap/Ras-specific GEF proteins that also include C3G (RAPGEF1), PDZ-GEF1 (RAPGEF2), PDZ-GEF2 (RAPGEF6), Repac (RAPGEF5), CalDAG-GEF1 (ARHGEF1), CalDAG-GEF3 (ARHGEF3), PLCε1 (PLCE1) and RasGEF1A, B, C. EPAC proteins consist of two structural lobes/halves connected by the so-called central "switchboard" region. (
  • Entropically favorable changes in protein dynamics have also been implicated in cAMP mediated EPAC activation. (
  • It conducts its function by activating its downstream effectors: protein kinase A (PKA), exchange proteins regulated by cAMP (EPAC) and cyclic nucleotide gated ion-channels. (
  • However, cAMP may also initiate signaling via a guanine nucleotide exchange protein directly activated by cAMP (Epac). (
  • Because ERK is involved in translational control of long-lasting plasticity and memory, our data suggest that Epac is a crucial link between cAMP and ERK during some forms of protein synthesis-dependent LTP. (
  • cAMP acts directly on three main targets: protein kinase A (PKA), the exchange protein activated by cAMP (Epac), and cyclic nucleotide-gated ion channels (CNGCs). (
  • Epac proteins function as guanine nucleotide exchange factors (GEFs) for both Rap1 and Rap2. (
  • Cyclic AMP (cAMP) activates both protein kinase A (PKA) and guanine-nucleotide exchange factor exchange protein directly activated by CAMP (EPAC)-mediated Ras-related Protein1 (RAP1) GTPase that regulates various cellular functions including cell migration. (
  • Cyclic AMP (Montrer APRT Anticorps ) (cAMP), a secondary messenger responsible for various physiological processes regulates cell metabolism by activating Protein kinase A (PKA) and by targeting exchange protein directly activated by cAMP ( EPAC ). (
  • Monocyte-to-macrophage differentiation with the cytokine granulocyte-macrophage colony-stimulating factor induces expression of the cyclic nucleotide phosphodiesterase PDE1B2. (
  • By contrast, Gα i/o can both modulate phosphodiesterase activity and inhibit adenylyl cyclase activity, reduce both intracellular cAMP levels and protein kinase A activity, leading to decreased depolarizing currents carried by HCN and L-type calcium channels. (
  • The large array of CaM targets identified to date includes protein kinases, the ubiquitous protein phosphatase calcineurin, adenyl cyclase, cyclic nucleotide phosphodiesterase, and cytoskeletal proteins such as spectrin and adducin. (
  • This gene encodes the gamma subunit of cyclic GMP-phosphodiesterase, which is composed of alpha- and beta- catalytic subunits and two identical, inhibitory gamma subunits. (
  • PDE6G (Phosphodiesterase 6G) is a Protein Coding gene. (
  • Gene Ontology (GO) annotations related to this gene include enzyme inhibitor activity and 3,5-cyclic-nucleotide phosphodiesterase activity . (
  • We report here that the cyclic GMP-inhibited cyclic AMP specific phosphodiesterase (PDE3B) is expressed as a membrane-bound protein in clonal insulin-secreting BRIN-BD11 cells. (
  • Secondly, the soluble guanylate cyclase (sGC), a major target of NO action, and cGMP-regulated enzymes like cGMP-dependent protein kinase and cyclic nucleotide gated channels are described. (
  • An additional focus of my research has been an investigation of enzymes (particularly those involved in turnover of endocannabinoids, hydrogen sulphide and cyclic nucleotides), as convergence points for signalling cross-talk, as well as quantifying enzyme activities ex vivo , for example, in pathological conditions or following drug exposure. (
  • Myelin is composed of a limited number of myelin proteins: proteolipid protein (PLP), myelin basic protein (MBP), 2′, 3′-cyclic nucleotide 3′-phosphohydrolase (CNPase), MAG, and several enzymes. (
  • NME4 is a protein kinases, which are enzymes that transfer a phosphate group from a phosphate donor, generally the g phosphate of ATP, onto an acceptor amino acid in a substrate protein. (
  • The existence of multiple divergent CaM isoforms in plants poses the question of whether or not they allow differential regulation of targets and can confer different Ca 2+ sensitivity to CaM-binding enzymes or proteins. (
  • Our study highlights that L. monocytogenes encodes a multitude of functional FtsW and RodA enzymes to produce its rigid cell wall and that their expression needs to be tightly regulated to maintain growth, cell division and antibiotic resistance. (
  • Two C-terminal cyclic nucleotide binding (CNB) domains cooperatively bind two molecules of cAMP, resulting in a conformational change of the R subunit that releases the active catalytic kinase subunit(s) from the inhibitory pseudo-substrate or substrate site of PKAR. (
  • We provide additional proof that ApoO indeed is a subunit of the MICOS and MIB complexes and propose the name Mic23 for this protein. (
  • CNB domains were first identified in the regulatory subunit of mammalian cAMP-dependent protein kinase (RI and RII). (
  • The PfPKAr subunit is normally predicted to possess 2 cyclic nucleotide binding domains. (
  • This induces an exchange of GDP for GTP on the G-protein α subunit and dissociation of the α subunit from the β γ heterodimer. (
  • Depending on its isoform, the GTP α subunit complex mediates intracellular signaling either indirectly by acting on effector molecules such as adenylate cyclase (AC) or phospholipase C (PLC), or directly by regulating ion channel or kinase function. (
  • Thus, the regulatory (R) subunit of PKA releases an active serine and threonine kinase upon binding to cAMP, and cAMP-bound Epacs promote the exchange of guanosine triphosphate (GTP) for guanosine diphosphate (GDP) on the small guanosine triphosphatases (GTPases) Rap1 and Rap2 ( 5 , 6 ). (
  • Similar complexes between ion channels, protein kinases, and protein phosphatases have been shown for several other channels ( Levitan 1999 ) and may be the rule rather than the exception. (
  • Protein phosphatases, also categorized into serine-threonine or tyrosine subfamilies, reverse the actions of protein kinases and serve critical functions in cell regulation. (
  • The energetic type of Rab protein, which contains GTP, can recruit particular binding partners such as for example sorting adaptors, tethering elements, kinases, motor and phosphatases proteins, and impact vesicle formation, transportation, and tethering [9C12]. (
  • VASP may also be involved in the intracellular signaling pathways that regulate integrin-extracellular matrix interactions. (
  • Different combinations of cytokines regulate signaling pathways that define the phenotype of the differentiated cell ( 4 , 5 ). (
  • We show that theobromine treatment elevates intracellular cAMP levels and increases the activity of p38 mitogen-activated protein kinase and c-Jun N-terminal kinase, whereas it attenuates p44/42 extracellular signal-regulated kinase activity and the Akt/mammalian target of rapamycin kinase and nuclear factor-kappa B signal pathways. (
  • The cyclic nucleotide binding (CNB) domain regulates signaling pathways in both eukaryotes and prokaryotes. (
  • Recognition of the various components in the cAMP-dependent signaling pathways that regulate microneme secretion during invasion provides book targets to stop erythrocyte invasion, inhibit bloodstream stage parasite development and stop malaria. (
  • Prompted by significant changes in the expression of genes involved in Ca 2+ and cyclic AMP (cAMP) signaling pathways in CAD-resistant MCF7 breast cancer cells, we identified here an early lysosomal Ca 2+ release through P2X purinergic receptor 4 (P2RX4) and subsequent Ca 2+ - and adenylyl cyclase 1 (ADCY1)-dependent synthesis of cAMP as a signaling route mediating CAD-induced lysosomal membrane permeabilization and cell death. (
  • The elevation of these two platelet cyclic nucleotides interferes with platelet activatory signalling pathways such as the intracellular Ca 2+ elevation and the reorganization of the cytoskeleton. (
  • Identification of the different elements in the cAMP-dependent signaling pathways that regulate microneme secretion during invasion provides novel targets to block erythrocyte invasion, inhibit blood stage parasite growth and prevent malaria. (
  • Using Trypanosoma and Leishmania as models, we currently focus on novel cAMP pathways and cAMP-independent protein kinase A (PKA) signalling. (
  • Many intracellular signaling pathways ultimately regulate gene expression. (
  • We therefore evaluated the role of phosphoinositide 3-kinase (PI3K) and p42/p44 mitogen-activated protein kinase (p42/p44 MAPK) pathways in regulating this enzyme. (
  • Taken together, these data demonstrate that cAMP/PKA and cAMP/EPAC1/RAP1-GTPase might inversely control cervical cancer cell migration, although both signaling pathways may up-regulate RAC1-GTPase. (
  • Information is therefore hypothesised to be encoded in these signals, which are decoded and relayed to downstream gene expression regulators and protein kinases via an array of Ca 2+ ‐binding sensor proteins. (
  • A large network of calcium‐binding proteins act as calcium sensors and relay calcium signals to downstream effector proteins. (
  • cAMP/cGMP frequently activate specific proteins kinases, which further regulate downstream signaling. (
  • cAMP-dependent protein kinase A (PKA) was identified as the major downstream effector of intracellular cAMP, acting as a cAMP sensor and in turn transducing cAMP-initiated signaling to further downstream cellular targets ( 2 , 3 ). (
  • Cyclic adenosine 3', 5'- monophosphate (cAMP) is a second messenger that functions through binding to its downstream targets protein kinase A (PKA), cyclic-regulated ion channels (CNG channels) and Epac1 (exchange protein directly activated by cAMP). (
  • Various effector proteins, including adaptor proteins implicated in modulation of the actin cytoskeleton, regulators of G proteins of the Rho family, and phospholipases, relay signaling downstream from Rap. (
  • These kinases phosphorylate downstream target proteins which mediate cGMP effects, e.g., by decreasing the intracellular calcium concentration. (
  • β-arrestin interacts with PDE4D5 and is a multifunctional protein that plays pivotal roles in signal transduction. (
  • Although the worm C. elegans may not much resemble humans, the molecules that regulate signal transduction in these two organisms prove to be quite similar. (
  • By this basic mechanism, protein kinases mediate most of the signal transduction in eukaryotic cells, regulating cellular metabolism, transcription, cell cycle progression, cytoskeletal rearrangement and cell movement, apoptosis, and differentiation. (
  • Ca 2+ is an important signal transduction molecule that has been shown to regulate responses to a large number of environmental stimuli in plants and control many developmental processes. (
  • Proteins and peptides that are involved in SIGNAL TRANSDUCTION within the cell. (
  • The longstanding interest of his laboratory is the role in intracellular signal transduction of multimolecular complexes organized by scaffold proteins. (
  • Paxillin is also a "docking" protein involved in organizing the signal transduction complex. (
  • Taken together, paxillin may function as a structural protein to maintain the integrity of the SMC contractile apparatus and as a docking protein to potentially mediate signal transduction for SMC contraction, migration, proliferation, and possibly differentiation. (
  • Signal transduction can alter neuronal function on vastly different time scales ranging from very rapid (millisecond) changes in membrane potential produced by ligand-gated channels to changes over seconds produced by intracellular second messengers and protein kinases. (
  • Activates retinal cGMP channels and thus discriminates between kinase and channel effects. (
  • A growth in cAMP activates proteins kinase A (PKA), which regulates microneme secretion. (
  • We demonstrate that buy 329907-28-0 publicity of merozoites to a minimal K+ environment as within bloodstream plasma activates the bicarbonate-sensitive cytoplasmic adenylyl cyclase (PfAC) resulting in a growth in cytosolic cAMP amounts and activation of proteins kinase A (PKA), which regulates microneme secretion. (
  • Increase in cAMP and cGMP concentration activates cyclic nucleotide gated channels (CNGC), which causes influx of Ca 2+ into the cytosol. (
  • Ca 2+ binding to calmodulin (CaM) and calcium‐dependent protein kinases (CDPK) indirectly activates the hypersensitive response (HR), defence‐related gene expression and increased salicylic acid (SA) production. (
  • β2-Adrenergic Receptor Lacking the Cyclic AMP-Dependent Protein Kinase Consensus Sites Fully Activates Extracellular Signal-Regulated Kinase 1/2 in Human Embryonic Kidney 293 Cells: Lack of Evidence for Gs/Gi Switching. (
  • Hypoxia-inducible factor 1 (HIF-1) activates the transcription of genes encoding proteins that enable cells to adapt to reduced O 2 availability. (
  • A rise in cAMP activates protein kinase A (PKA), which regulates microneme secretion. (
  • We demonstrate that exposure of merozoites to a low K + environment as found in blood plasma activates the bicarbonate-sensitive cytoplasmic adenylyl cyclase β (PfACβ) leading to a rise in cytosolic cAMP levels and activation of protein kinase A (PKA), which regulates microneme secretion. (
  • However, expression of PDE1B2 short hairpin RNA effectively suppresses PDE1B2 mRNA, protein, and activity up-regulation. (
  • Using the HL-60 PDE1B2 knockdown cells and agonists for either adenylyl or guanylyl cyclase, it was found that PDE1B2 predominantly regulates cGMP and plays a lesser role in cAMP regulation in response to cyclase agonists. (
  • Protein kinase A (PKA), the main effector of cAMP in eukaryotes, is a paradigm for the mechanisms of ligand-dependent and allosteric regulation in signalling. (
  • 7500 members that confers ligand-dependent allosteric regulation to a diverse range of proteins 2 . (
  • Hanks and Hunter were the first to report that sequence similarity of kinase catalytic domains reflects protein kinase function and/or mode of regulation ( 3 , 4 ). (
  • SUMOylation of proteins is an important method of regulation. (
  • Down-regulation of Prkar1a by up to 70% was achieved in transgenic mouse tissues and embryonic fibroblasts, with concomitant changes in kinase activity and increased cell proliferation, respectively. (
  • Maronde E, Saade A, Ackermann K, Goubran-Botros H, Pagan C, Bux R, Bourgeron T, Dehghani F, Stehle JH (2011) Dynamics in enzymatic protein complexes offer a novel principle for the regulation of melatonin synthesis in the human pineal gland. (
  • Farnesol suppresses the resistance of C. albicans biofilms to antifungals by regulating the expression of the gene CYR1 and PDE2 , while PDE2 regulation was subordinate to CYR1 regulation. (
  • Physiological regulation of G protein-linked signaling. (
  • In this comprehensive review, the structure, function, regulation, and biological consequences of natriuretic peptides and their associated signaling proteins are described. (
  • cAMP can perform its regulation in cellular transport through the binding to cAMP dependent protein kinases (PKAs), cAMP-activated guanine exchange factors (EPACs) and cyclic nucleotide-gated channels functioning in transduction of sensory signals (CNGs). (
  • The functional relevance of this interaction is still unclear, but the mere fact that Epac1 only binds to the active form of Ezrin/Radixin indicates that activation of these proteins is a crucial step in the spatial regulation of Epac1. (
  • THE small calcium sensor protein calmodulin (CaM) is one of the major mediators of the complex interactions that underlie calcium regulation (see V an E ldik and W atterson 1998 for review). (
  • The brain contains numerous other types of protein serine-threonine kinases that also play important roles in the regulation of cell function. (
  • Recent research suggests that cAMP also affects the function of higher-order thinking in the prefrontal cortex through its regulation of ion channels called hyperpolarization-activated cyclic nucleotide-gated (HCN) channels. (
  • In the pituitary, gonadotropin synthesis and release is a highly regulated process that involves coordinated gene expression and protein synthesis in conjunction with acute regulation of secretion (12). (
  • Ali R, Zielinski RE and Berkowitz GA (2006) Expression of plant cyclic nucleotide‐gated cation channels in yeast. (
  • When cGMP is elevated in these cells, it is not only broken down at the catalytic site of PDE5, but it also binds to cGMP-selective sites on several types of proteins, including cGMP-dependent protein kinase (PKG), cGMP-gated cation channels, and allosteric sites on PDE5. (
  • This work further demonstrates the relative simplicity with which the potency and activity of cyclic peptides identified from SICLOPPS libraries can be optimized. (
  • Design of Cyclic Peptides as Protein Recognition Motifs. (
  • Intracellular Signaling Peptides and Proteins" is a descriptor in the National Library of Medicine's controlled vocabulary thesaurus, MeSH (Medical Subject Headings) . (
  • This graph shows the total number of publications written about "Intracellular Signaling Peptides and Proteins" by people in Harvard Catalyst Profiles by year, and whether "Intracellular Signaling Peptides and Proteins" was a major or minor topic of these publication. (
  • Below are the most recent publications written about "Intracellular Signaling Peptides and Proteins" by people in Profiles. (
  • They can take many forms, including soluble and cell‐bound ligands (proteins, lipids, peptides or small molecules) and insoluble matrix substrates, but to act as guidance cues, they must be presented to the cell in a spatially restricted manner. (
  • Natriuretic peptides are a family of structurally related but genetically distinct hormones/paracrine factors that regulate blood volume, blood pressure, ventricular hypertrophy, pulmonary hypertension, fat metabolism, and long bone growth. (
  • cGMP-induced effects are regulated by endogenous receptor ligands such as nitric oxide (NO) and natriuretic peptides (NPs). (
  • Accordingly, inhibition of the upstream kinases of ERK 1/2 by 2′-amino-3′-methoxyflavone (PD98059) not only suppressed MAPK activation caused by FK but also abolished the survival promoting activity that this compound exerts on TH + neurons. (
  • extracellular signal-regulated kinase [ERK] 1/2 and c-Jun N-terminal kinase [JNK] 1/2, but not p38 MAPK) in collagen-activated platelets. (
  • Extracellular signal-regulated kinase (ERK) is a member of the mitogen-activated protein kinase (MAPK) family, with protean functional roles in cell physiology ( 9 ). (
  • Activation of immediate-early genes by GnRH receptor signaling is dependent on mitogen-activated protein kinase (MAPK) signaling, particularly through MAPK1/3 [also extracellular signal-regulated kinase (ERK) 2/1], which also modulates the translational machinery to increase protein synthesis (12, 21, 22). (
  • In mammalian cells, the cAMP reactive PKA, which regulates different cellular procedures in response to a growth in cytosolic cAMP amounts, comprises two catalytic subunits and two regulatory subunits [7]. (
  • 4 5 6 Paxillin can directly associate with cytosolic protein tyrosine kinases, csk, crk, c-src, and focal adhesion kinase (FAK). (
  • Cyclic GMP (cGMP) signalling regulates multiple biological functions through activation of protein kinase G and cyclic nucleotide-gated (CNG) channels. (
  • Our analysis found that several ion channels and a class of thioesterases constitute the possible cyclic nucleotide binding proteins in plants. (
  • Cyclic nucleotide-gated (CNG) channels are crucial for sensory transduction in rod and cone photoreceptors and olfactory sensory neurons. (
  • Selective activator of both, cGMP-dependent protein kinase type I α and type II, as well as of cGMP-gated ion channels. (
  • Cyclic nucleotide-gated channels (CNGCs) are cationic-permeable ion channels. (
  • These include the Rap guanine nucleotide exchange factors (GEFs) Epac1 and Epac2 ( 5 , 6 ) and the hyperpolarization-activated potassium (HCN) and calcium (CNGC) cyclic nucleotide-gated channels ( 7 , 8 ). (
  • As a result, cAMP-regulated effectors such as hyperpolarization-activated cyclic nucleotide-gated cation (HCN) channels, delayed rectifier, and voltage-gated Ca 2+ channels are enlisted by sympathetic activity to increase pacemaker cell firing rate. (
  • Several effects, mediated by both Gα i/o and Gβγ subunits, may contribute to this reduction in HR. Gβγ heterodimers directly activate G protein-coupled inward rectifying potassium (GIRK) channels, resulting in membrane hyperpolarization. (
  • More recently, calcium channels and calcium-regulated channels have proved to be CaM targets (reviewed in S aimi and K ung 2002 ). (
  • Although second messengers such as cyclic nucleotides and Ca 2+ may directly gate ion channels, their major role in intracellular signaling systems is to regulate protein serine-threonine kinases that phosphorylate other proteins. (
  • Köhler, C. & Neuhaus, G. 1998 Cloning and partial characterization of two putative cyclic nucleotide-regulated ion channels from Arabidopsis thaliana , designated CNGC1 (Y16327) and CNGC, 2 (Y 16328). (
  • Ras proteins are small GTPases that regulate important cellular signaling cascades to control cell growth, proliferation, and differentiation ( 1 ). (
  • EPAC1 is a multifunctional protein whose cellular functions are tightly regulated in spatial and temporal manners. (
  • Through interactions with an array of cellular partners, EPAC1 has been shown to form discrete signalsomes at plasma membrane, nuclear-envelope, and cytoskeleton, where EPAC1 regulates numerous cellular functions. (
  • Protein-protein interactions (PPIs) are indispensable in almost all cellular processes. (
  • The R 2 homodimer is formed by an N-terminal dimerization/docking (DD) domain that also mediates sub-cellular localization via A kinase anchoring proteins (AKAPs). (
  • Elevation of intracellular cyclic AMP levels leads to diverse cellular responses dependent on the cell type. (
  • cAMP regulates cellular functions primarily by activating PKA. (
  • cAMP is an ubiquitous second messenger that transduces signals from a variety of hormones, neurotransmitters, and inflammatory mediators to regulate a large number of key cellular processes. (
  • Although it is generally accepted that many NO effects are mediated via elevation of intracellular cGMP, one should keep in mind that NO can exert effects independent of cGMP production, for instance via modification of cellular proteins by S-nitrosylation of cysteine residues. (
  • Among them, multifunctional CaMKII, a well-characterized kinase that can phosphorylate a broad range of proteins upon binding to Ca 2+ /CaM, is thought to play an important role in a variety of cellular events in mammals ( Colbran and Soderling, 1990 ). (
  • The BH3-only family of proteins is key for initiating apoptosis in a variety of contexts, and may also contribute to non-apoptotic cellular processes. (
  • Despite their important role in initiating programmed cell death and likely other cellular processes, our understanding of the factors that regulate BH3-only proteins is incomplete. (
  • As a secondary messenger, cAMP can regulate plenty of cellular activities. (
  • Protein-protein interactions are ubiquitous, essential to almost all known biological processes, and offer attractive opportunities for therapeutic intervention. (
  • Cyclic nucleotides are ubiquitous intracellular messengers. (
  • The ubiquitous presence of cyclic nucleotides may be due to several characteristics which make it an ideal second messenger. (
  • Scripts were written for reassembly of contiguous exons identified from genomic sequence to generate the predicted catalytic domain sequence of each kinase. (
  • The family has been classified in 8 major groups based on sequence comparison of their tyrosine (PTK) or serine/threonine (STK) kinase catalytic domains. (
  • NtCaMK1 has all 11 subdomains of a kinase catalytic domain, lacks EF hands for Ca 2+ -binding, and is structurally similar to other CaMKs in mammal systems. (
  • Not only are they allosterically regulated by cGMP at non‐catalytic sites, they also hydrolyze cGMP to 5′‐GMP. (
  • Contrary to some reports, we found no biochemical or bioinformatic evidence for a plant cyclic nucleotide regulated protein kinase, suggesting that cyclic nucleotide functions in plants have evolved differently than in mammals. (
  • These affinity and activation measurements show that beta-phenyl-1,N2-ethenoguanosine 3',5'-monophosphate (PET-cGMP) is most selective for PKG I, whereas 8-(4-chlorophenylthio)guanosine-3'-5'-cyclic monophosphate (8-pCPT-cGMP) is most selective for PKG II. (
  • The first immunoassays for cyclic nucleotides were published in the early 1970's, and the introduction of commercially available radioactively labeled cAMP and cGMP allowed the measurement of cyclic AMP and GMP at lower and lower concentrations. (
  • Using supraoptic nuclei in brain slices from lactating rats, we examined the involvement of extracellular signal-regulated protein kinase 1/2 (ERK1/2) and filamentous actin (F-actin) in burst generation by oxytocin (OT) neurons. (
  • Phosphorylated extracellular signal-regulated protein kinase 1/2 (pERK1/2) and actin cytoskeleton are strong candidates for burst transition. (
  • The persistence of this form of LTP requires extracellular signal-regulated protein kinase (ERK) and new protein synthesis, but not transcription. (
  • Ena, the founding member of the family was discovered in a drosophila genetic screen for mutations that act as dominant suppressors of the abl non receptor tyrosine kinase . (
  • Growth element receptor-bound proteins 14 (Grb14) can be an adapter proteins implicated in receptor tyrosine kinase signaling. (
  • mouse research also expose the results of Grb14 on receptor tyrosine kinase signaling inside a tissue-specific way. (
  • The Arabidopsis cyclic nucleotide-gated channel (CNGC) family consists of 20 members, which have been reported to participate in various physiological processes, such as pathogen defense, development, and thermotolerance. (
  • The DRUGSFORD project has generated a large number of new cGMP analogues (cyclic nucleotides) to efficiently bind and inhibit the cGMP targets, i.e. protein kinase G (PKG) and the cyclic nucleotide gated channel (CNGC). (
  • With an understanding of the protein domains which can bind cyclic nucleotides (CNB and GAF domains) we scanned the completed genomes of the higher plants Arabidopsis thaliana (mustard weed) and Oryza sativa (rice) for the effectors of these signalling molecules. (
  • In order to further explore the roles of cyclic nucleotides in plants, we performed a bioinformatics based analysis of the completed Arabidopsis thaliana and Orzya sativa genomes [ 21 - 23 ] in order to elucidate the potential targets of cyclic nucleotides in plants. (
  • All named proteins are from Arabidopsis thaliana . (
  • 2007) Death don't have no mercy and neither does calcium: Arabidopsis cyclic nucleotide gated channel2 and innate immunity. (
  • Protein kinase G (PKG) is activated by nitric oxide (NO)-induced cGMP binding or alternatively by oxidant-induced interprotein disulfide formation. (
  • The GTP-bound energetic type of Rab could be recruited to membrane vesicles, where it promotes membrane trafficking by getting together with UNC-1999 supplier particular effector proteins (Shape 1A) [18,19]. (
  • Hepatitis c virus infection in the case for a serine or threonine kinases cyclic nucleotide regulated camp-dependent protein kinases (countinued) yeast cyclic nucleotide. (
  • The existence of eukaryotic CNB domains not associated with binding of cyclic nucleotides suggests that orphan CNB domains in other eukaryotes may bind undiscovered signalling molecules. (
  • The trypanosome model again serves as vanguard to explore novel biochemisty: the existence of eukaryotic cyclic nucleotide binding (CNB) domains with alternative binding specificity suggests that there might also be orphan CNB domains in other eukaryotes regulated by yet undiscovered signalling molecules. (
  • Ena-VASP family members contain an N-terminal EVH1 domain that binds proteins containing E/DFPPPPXD/E motifs and targets Ena-VASP proteins to focal adhesions cell membranes. (
  • Cyclic peptide libraries have successfully been employed for the identification of inhibitors of highly challenging targets. (
  • Our PKA-induced phosphoproteome identified numerous PKA targets that match the role of this kinase in cell division, motility and development of the parasite. (
  • Development of a Cyclic Peptide Inhibitor of the p6/UEV Protein-Protein Interaction. (
  • We report the development of a cyclic peptide inhibitor of the p6/UEV interaction, from a non cell-permeable parent that was identified in a SICLOPPS screen. (
  • Potent selective inhibitor of protein kinase G I a, I ß and especially of type II. (
  • Bath application of the generic protein kinase inhibitor and a selective PKG inhibitor, H-7 and KT-5823, respectively, reduced the frequency of the rhythm, suggesting that PKG acted as a target for cGMP. (
  • 22 Increased expression of NAD(P)H oxidase subunits, enhanced NAD(P)H oxidase, and protein kinase C activity as well as increased levels of the endogenous eNOS inhibitor asymmetrical dimethylarginine result in enhanced oxidative stress and reduced NO bioavailability in diabetes. (
  • This was shown using SKF94836 (PDE3 inhibitor) which maximally inhibited membrane-bound cyclic AMP PDE activity by approximately 25-30% and by RT-PCR. (
  • The crystal structure from the tyrosine kinase domain from the IR in AV-412 complicated using the IR-interacting domain of Grb14 revealed that Grb14 works as a pseudosubstrate inhibitor of IR kinase by getting together with its substrate binding groove and therefore functions like a selective inhibitor of insulin signaling (13). (
  • De Rooij and colleagues performed a database search for proteins with sequence homology to both GEFs for Ras and Rap1 and to cAMP-binding sites, which led to the identification and subsequent cloning of RAPGEF3 gene. (
  • Epac1 is guanine nucleotide exchange factor toward both Rap1 and Rap2. (
  • Results: Here we report the characterization of a novel opsin family from these green algae: light-inhibited guanylyl cyclases regulated through a two-component-like phosphoryl transfer, called "two-component cyclase opsins" (2c-Cyclops). (
  • We show here that K-Ras is a substrate for cyclic GMP-dependent protein kinases (PKGs). (
  • Studying length variations in protein domains, which have been introduced by indels (insertions/deletions), are important because theses indels act as evolutionary signatures in introducing variations in substrate specificity, domain interactions and sometimes even regulating protein stability. (
  • the TKs (tyrosine kinases) and the TKLs (tyrosine kinase-like kinases). (
  • The Src-family tyrosine kinase Fyn is involved in the initial events of myelination. (
  • experiments show that Grb14 impairs the tyrosine kinase activity of the IR toward exogenous substrates and protects the phosphorylated tyrosine residues from proteins tyrosine phosphatase 1B (PTP1B) activity (5). (
  • Photoaffinity palladium reagents for capture of protein-protein interactions. (
  • My research group at LMU is interested in signalling events regulating parasite development, metabolic adaptations and host-parasite interactions. (
  • 6 10 SH2, together with SH3 and the LIM domains (a conserved sequence of Lin-11, IsI-1, and Mec-3) of paxillin, mediates protein-protein interactions. (
  • PTEN induced kinase 1 (PINK1) is a serine/threonine kinase in the outer membrane of mitochondria (OMM), and known as a responsible gene of Parkinson's disease (PD). (
  • coli, and the purified fusion protein was found capable of autophosphorylation on serine and threonine residues. (
  • An serine-threonine protein kinase that requires the presence of physiological concentrations of CALCIUM and membrane PHOSPHOLIPIDS. (
  • A cDNA encoding a calcium (Ca 2+ )/calmodulin (CaM)-dependent protein kinase (CaMK) from tobacco ( Nicotiana tabacum ), NtCaMK1 , was isolated by protein-protein interaction-based screening of a cDNA expression library using 35 S-labeled CaM as a probe. (
  • The calcium/calmodulin-dependent kinase (CAMK) group consists of 75 kinases regulated by Ca2+/CaM and close relative family (CAMK, CAMKL, DAPK, MAPKAPK). (
  • We show here that the null behavioral phenotype originates in the nervous system and involves a CaM function that requires calcium binding to all four sites of the protein. (
  • Two pairs of EF-hand-type calcium-binding sites are present in each of its two globular domains and conformational changes produced by calcium binding dramatically alter the target interaction properties of the protein. (
  • The up-regulated genes were most likely involved in calcium transportation, as well as synthesis and secretory activities of ions and molecules, reflecting the peak stage of eggshell formation. (
  • Several effectors of cGMP have been identified, most importantly cGMP-regulated protein kinases (abbreviated as cGKs or PKGs). (
  • Furthermore to dealing with many tethering effectors at vesicle tethering stage, Rab proteins are also involved with rules of SNARE proteins reliant fusion of vesicles. (
  • Vasodilator-stimulated phosphoprotein is a protein that in humans is encoded by the VASP gene. (
  • Rap guanine nucleotide exchange factor 3 also known as exchange factor directly activated by cAMP 1 (EPAC1) or cAMP-regulated guanine nucleotide exchange factor I (cAMP-GEFI) is a protein that in humans is encoded by the RAPGEF3 gene. (
  • Cyclic AMP receptor protein was originally identified as a catabolite gene activator protein. (
  • Here we show that Fyn stimulates transcription of the myelin basic protein (MBP) gene for myelination. (
  • With more than 500 gene products, the protein kinase family is one of the largest families of proteins in eukaryotes. (
  • Human coagulation factor-III protein (295 aa, 33 kDa precursor) is encoded by the human coagulation factor III (thromboplastin, tissue factor) (F3) gene. (
  • Protein restriction is difficult to classify the leukemia type, gene expression (sage) has been suggested as an alternative to standard doses. (
  • All their attempts to link the gene products to cAMP-regulated kinase activity failed. (
  • eNOS gene transfer showed no effect on paxillin downregulation 2 days after injury but significantly enhanced the recovery of paxillin protein 5 days and 2 weeks after injury. (
  • Vinculin, a paxillin-binding protein, was not altered by vascular injury or by eNOS gene transfer. (
  • Eukaryotic cells increase the diversity of proteins that can be produced from a single gene by alternatively splicing the exons within the primary transcript. (
  • The down-regulated genes annotated to Gene Ontology (GO) terms showed anion transport, synaptic vesicle localisation, organic anion transport, secretion and signal release as the five most enriched terms. (
  • While the expression level of the calbindin gene increases during the ovulatory cycle at a time coincident with eggshell calcification, there is little or no change in the tissue levels of calbindin protein, indicating post-translational control of calbindin levels [ 4 ]. (
  • Aiba, H. , Fujimoto, S. , Ozaki, N. 1982 Molecular cloning and nucleotide sequencing of the gene for E. coli cAMP receptor protein. (
  • The N terminal regulatory lobe is responsible for cAMP binding while the C-terminal lobe contains the nucleotide exchange factor activity. (
  • Hence, the synonym cAMP-dependent protein kinase is commonly used. (
  • Based on the PDE2 crystal structure 11 residues were proposed to be involved in cyclic nucleotide binding [ 18 ], but comparison to the cAMP binding GAF domain of the Anabaena adenylate cyclase shows that these residues may only be strictly conserved in mammals. (
  • cAMP is a partial agonist for PKG , and we elucidate the mechanism for cAMP partial agonism through the comparative NMR analysis of the apo (show C9orf3 ELISA Kits ), cGMP-, and cAMP-bound forms of the PKG cyclic nucleotide-binding domain B. (
  • Stable isotope labeling was used to confidently identify and differentially quantify target proteins and their preferential binding affinity for the three different cAMP analogs. (
  • cAMP can influence cell growth, differentiation, and movement as well as regulating specialized actions unique to specific cell types. (
  • The principal target of cAMP is cAMP-dependent protein kinase (PKA) 1 . (
  • Interestingly, localized pools of cAMP regulate defined physiological events. (
  • Right here, we demonstrate that cAMP acts as an integral regulator that handles the well-timed secretion of microneme protein during invasion. (
  • Surprisingly, the archetypal cAMP-dependent protein kinase was apparently not responsible for ERK 1/2 activation. (
  • found that the cAMP-activated kinase PKA phosphorylated HIF-1α, which increased its abundance and activity in cultured cardiomyocytes and a cancer cell line. (
  • Here, we demonstrate that cAMP serves as a key regulator that controls the timely secretion of microneme proteins during invasion. (
  • We found that the Rap guanine nucleotide exchange factor Rapgef2 was enriched from primary bovine neuroendocrine cells by cAMP-agarose affinity chromatography and that it was specifically eluted by cAMP. (
  • In a difficult problem in the eyes, occasional lacrimation, slight stickiness of the protein kinases yeast cyclic nucleotide regulated camp-dependent protein kinases. (
  • In this paper, we show that protein kinase A (PKA) of trypanosomatids is not regulated by cAMP but by nucleoside analogues. (
  • Not surprising, a large body of evidence was required to challenge the corollary that all PKA orthologues are cAMP-dependent or at least cyclic nucleotide-dependent protein kinases. (
  • Protein kinase A is a cAMP dependent kinase in all known eukaryotes except kinetoplastids. (
  • With negative data in hand and some reports of cAMP-dependent kinase activity in the related kinetoplastids T. cruzi and Leishmania , we were obviously not in a position to publish the observation. (
  • Susanne Kramer then started functional analysis of that unusual PKA as her PhD project and developed an in vivo kinase reporter assay to exclude all the possible technical reasons for lack of response to cAMP. (
  • One drug (dipyridamole) she used to increase intracellular cAMP surprisingly induced kinase activity, in contrast to all other approaches. (
  • ADCY1 is responsible for catalyzing ATP to cyclic AMP (cAMP). (
  • The advent of direct assays for cAMP and cGMP, which allow the cyclic nucleotides to be measured in cells and tissues without the need for lengthy pretreatment steps, now allows the measurement of femtomoles of these molecules in just a few hours. (
  • The optimal EAA-containing protein format necessary to maximally stimulate muscle protein synthesis and optimize whole-body net protein balance during caloric deprivation has not been dete. (
  • They activate protein kinases by regulating cyclic nucleotide synthesis. (
  • The down-regulated genes at 15 h relative to the 5 h time-point were most likely involved in the transport of molecules and synthesis activities, initiating the formation of the eggshell. (
  • It was subsequently shown to regulate several functions unrelated to catabolism, and to be both a negative and a positive regulator of transcription. (
  • The region responsible for the transactivation by Fyn is located between nucleotides −675 and −647 with respect to the transcription start site. (
  • A more in-depth analysis has been performed on the 535 worm proteins containing zinc-binding domains, including the C4, C2H2, and C3HC4 ring finger types ( 3 ), and on the 83 worm homeobox transcription factors ( 4 ). (
  • We used genetic screening and epistasis analysis to determine that its transcription is regulated in URX by neuronal activity and/or in parallel by orthologs of Protein Kinase G and the Salt-Inducible Kinase family. (
  • Thus, these data establish a mechanistic link between a kinase (PKA) and transcription factor (HIF-1) that contribute to the progression of cancer and cardiovascular disease. (
  • Transcription is stimulated when an activator protein displaces nucleosomes, the major component of chromatin, permitting a complex of proteins, called general transcription factors, to bind DNA at a core promoter and recruit RNA polymerase. (
  • DNA-binding sites for regulatory proteins are called regulatory elements, and the proteins that bind them are called transcription factors. (
  • HL-60 cells treated with phorbol-12-myristate-13-acetate differentiate to a macrophage-like phenotype and up-regulate PDE1B2. (
  • Furthermore, in intact HL-60 cells, PDE1B2 activity can be regulated by changes in Ca +2 levels. (
  • HIV from infected cells is driven by the protein-protein interaction between the p6 domain of the HIV Gag protein and the UEV domain of the human TSG101 protein. (
  • The merozoites invade fresh red blood cells, a process that involves shedding of a microneme protein called apical membrane antigen-1 (AMA1) from the merozoite surface. (
  • Optogenetic approaches using light-activated proteins like Channelrhodopsin-2 (ChR2) enable investigating the function of populations of neurons in live Caenorhabditis elegans (and other) animals, as ChR2 expression can be targeted to these cells using specific promoters. (
  • Until recently, the roles of cyclic nucleotides in plant cells have proven difficult to uncover. (
  • Stimulation of the β 2 -adrenergic receptor (β 2 AR) in human embryonic kidney (HEK) 293 cells causes a transient activation of Extracellular Signal-Regulated Kinase (ERK) 1/2. (
  • Patching with antibiotic prophylaxis for the env-encoded protein of the internal limiting membrane of cells were fused with nonmalignant cells, most of patients with specific nuclear localization. (
  • The fact that light reduces the levels of cyclic AMP in dark-adapted cone-dominant retinas suggests an analogy between the function of cyclic GMP in rod photoreceptors and of cyclic AMP in cone visual cells. (
  • Finally, RGS4-null SAN cells showed decreased levels of G protein-coupled inward rectifying potassium (GIRK) channel desensitization and altered modulation of acetylcholine-sensitive potassium current ( I KACh ) kinetics following carbachol stimulation. (
  • These proteins have recently emerged as inhibitory candidates of parasympathetic signaling in autorhythmic cells of the SAN because expression of RGS-resistant Gα i2 or Gα o in mice reduced pacemaker cell automaticity. (
  • Importantly, the microvillar localization is through binding to Ezrin/Radixin, proteins that function as linkers between the actin cytoskeleton and the apical membrane of polarized cells and as scaffold protein for protein complexes. (
  • SNAREs, which were initially identified in neuronal cells for their function in membrane fusion ( 5 ), include vesicular SNAREs such as vesicle-associated membrane proteins, target membrane SNAREs (t-SNAREs) such as syntaxins, and the Sec1/Munc18 family of proteins that serve as binding partners of t-SNAREs. (
  • Kurosaki, F. , Kaburaki, H. , Nishi, A. 1994 Involvement of plasma membrane-located calmodulin in the response decay of cyclic nucleotide-gated cation channel of cultured carrot cells. (
  • Eukaryotic protein kinases can be classified into distinct, well-characterized groups based on amino acid sequence similarity and function. (
  • The Kinomer v. 1.0 database presented here contains annotated classifications for the protein kinase complements of 43 eukaryotic genomes. (
  • The currently accepted classification of the eukaryotic protein kinase superfamily considers eight 'conventional' protein kinase groups (ePKs) and four 'atypical' groups (aPKs) ( 5 , 6 ). (
  • The sequencing of complete genomes for many eukaryotic species has allowed the determination and comparison of their complete kinase complements (kinomes). (
  • Genetic Selections with SICLOPPS Libraries: Toward the Identification of Novel Protein-Protein Interaction Inhibitors and Chemical Tools. (
  • Although regulators of G protein signaling (RGS) proteins are potent inhibitors of Gα i/o signaling in many tissues, the RGS protein(s) that regulate parasympathetic tone in the SAN are unknown. (