A type I cAMP-dependent protein kinase regulatory subunit that plays a role in confering CYCLIC AMP activation of protein kinase activity. It has a lower affinity for cAMP than the CYCLIC-AMP-DEPENDENT PROTEIN KINASE RIBETA SUBUNIT.
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.
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 family of enzymes that catalyze the conversion of ATP and a protein to ADP and a phosphoprotein.
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.
The introduction of a phosphoryl group into a compound through the formation of an ester bond between the compound and a phosphorus moiety.
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)
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.
Agents that inhibit PROTEIN KINASES.
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 monomeric calcium-calmodulin-dependent protein kinase subtype that is expressed in a broad variety of mammalian cell types. Its expression is regulated by the action of CALCIUM-CALMODULIN-DEPENDENT PROTEIN KINASE KINASE. Several isoforms of this enzyme subtype are encoded by distinct genes.
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.
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.
A group of enzymes that catalyzes the phosphorylation of serine or threonine residues in proteins, with ATP or other nucleotides as phosphate donors.
A group of cyclic GMP-dependent enzymes that catalyze the phosphorylation of SERINE or THREONINE residues of proteins.
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.
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.
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.
The rate dynamics in chemical or physical systems.
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.
Structurally related forms of an enzyme. Each isoenzyme has the same mechanism and classification, but differs in its chemical, physical, or immunological characteristics.
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).
Established cell cultures that have the potential to propagate indefinitely.
A species of ciliate protozoa. It is used in biomedical research.
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.
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.
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 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.
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.
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 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.
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)
A phorbol ester found in CROTON OIL with very effective tumor promoting activity. It stimulates the synthesis of both DNA and RNA.
The sequence of PURINES and PYRIMIDINES in nucleic acids and polynucleotides. It is also called nucleotide sequence.
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.
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.
A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.
Tumors or cancer of the COLON.
Human colonic ADENOCARCINOMA cells that are able to express differentiation features characteristic of mature intestinal cells such as the GOBLET CELLS.
A family of gastrointestinal peptide hormones that excite the secretion of GASTRIC JUICE. They may also occur in the central nervous system where they are presumed to be neurotransmitters.
A cell line derived from cultured tumor cells.
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.
An immunoassay utilizing an antibody labeled with an enzyme marker such as horseradish peroxidase. While either the enzyme or the antibody is bound to an immunosorbent substrate, they both retain their biologic activity; the change in enzyme activity as a result of the enzyme-antibody-antigen reaction is proportional to the concentration of the antigen and can be measured spectrophotometrically or with the naked eye. Many variations of the method have been developed.
Commercially prepared reagent sets, with accessory devices, containing all of the major components and literature necessary to perform one or more designated diagnostic tests or procedures. They may be for laboratory or personal use.
Binary classification measures to assess test results. Sensitivity or recall rate is the proportion of true positives. Specificity is the probability of correctly determining the absence of a condition. (From Last, Dictionary of Epidemiology, 2d ed)
Common name for the species Gallus gallus, the domestic fowl, in the family Phasianidae, order GALLIFORMES. It is descended from the red jungle fowl of SOUTHEAST ASIA.
A genus of deer, Rangifer, that inhabits the northern parts of Europe, Asia, and America. Caribou is the North American name; reindeer, the European. They are often domesticated and used, especially in Lapland, for drawing sleds and as a source of food. Rangifer is the only genus of the deer family in which both sexes are antlered. Most caribou inhabit arctic tundra and surrounding arboreal coniferous forests and most have seasonal shifts in migration. They are hunted extensively for their meat, skin, antlers, and other parts. (From Webster, 3d ed; Walker's Mammals of the World, 5th ed, p1397)
Immunoglobulin molecules having a specific amino acid sequence by virtue of which they interact only with the ANTIGEN (or a very similar shape) that induced their synthesis in cells of the lymphoid series (especially PLASMA CELLS).
The property of antibodies which enables them to react with some ANTIGENIC DETERMINANTS and not with others. Specificity is dependent on chemical composition, physical forces, and molecular structure at the binding site.
Antibodies produced by a single clone of cells.
Immunoglobulins produced in response to VIRAL ANTIGENS.
Immunoglobulins produced in a response to BACTERIAL ANTIGENS.

Increased expression of the RIalpha subunit of the cAMP-dependent protein kinase A is associated with advanced stage ovarian cancer. (1/164)

The primary element in the cAMP signal transduction pathway is the cAMP-dependent protein kinase (PKA). Expression of the RIalpha subunit of type I PKA is elevated in a variety of human tumours and cancer cell lines. The purpose of this study was to assess the prognostic importance of RIalpha expression in patients with ovarian cancer. We have evaluated the expression of RIalpha in a panel of human ovarian tumours (n = 40) and five human ovarian cancer cell lines using quantitative reverse transcription polymerase chain reaction (RT-PCR) and Western blot analysis. The human ovarian cell lines OAW42 and OTN14 express high endogenous levels of RIalpha mRNA and protein (at significantly higher mRNA levels than high tissue expressors, P < 0.05). The ovarian cell line A2780 expresses low endogenous levels of RIalpha mRNA and protein (also at higher mRNA levels than low tissue expressors, P < 0.05). Quantitative RT-PCR revealed no significant difference in RIalpha mRNA expression between different ovarian histological subtypes in this study. No associations were found between RIalpha mRNA expression and differentiation state. RIalpha mRNA expression was significantly associated with tumour stage (P = 0.0036), and this remained significant in univariate analysis (P = 0.0002). A trend emerged between RIalpha mRNA expression levels and overall survival in univariate analysis (P = 0.051), however, by multivariate analysis, stage remained the major determinant of overall survival (P = 0.0001). This study indicates that in ovarian epithelial tumours high RIalpha mRNA expression is associated with advanced stage disease. RIalpha expression may be of predictive value in ovarian cancer and may be associated with dysfunctional signalling pathways in this cancer type.  (+info)

Diminished levels of protein kinase A RI alpha and RI beta transcripts and proteins in systemic lupus erythematosus T lymphocytes. (2/164)

Deficient type I protein kinase A phosphotransferase activity occurs in the T cells of 80% of subjects with systemic lupus erythematosus (SLE). To investigate the mechanism of this deficient isozyme activity, we hypothesized that reduced amounts of type I regulatory (RI) isoform transcripts, RIalpha and RIbeta, may be associated with a diminution of RIalpha and/or RIbeta protein. Sixteen SLE subjects with a mean (+/-1 SD) SLE disease activity index of 12.4 +/- 7.2 were studied. Controls included 16 normal subjects, six subjects with primary Sjogren's syndrome (SS), and three subjects with SS/SLE overlap. RT-PCR revealed that normal, SS, SS/SLE, and SLE T cells expressed mRNAs for all seven R and catalytic (C) subunit isoforms. Quantification of mRNAs by competitive PCR revealed that the ratio of RIalpha mRNA to RIbeta mRNA in normal T cells was 3.4:1. In SLE T cells there were 20 and 49% decreases in RIalpha and RIbeta mRNAs (RIbeta; p = 0.008), respectively, resulting in an RIalpha:RIbeta mRNA of 5.3:1. SS/SLE T cells showed a 72.5% decrease in RIbeta mRNA compared with normal controls (p = 0.01). Immunoblotting of normal T cell RIalpha and RIbeta proteins revealed a ratio of RIalpha:RIbeta of 3.2:1. In SLE T cells, there was a 30% decrease in RIalpha protein (p = 0.002) and a 65% decrease in RIbeta protein (p < 0.001), shifting the ratio of RIalpha:RIbeta protein to 6.5:1. T cells from 25% of SLE subjects lacked any detectable RIbeta protein. Analysis of several lupus T cell lines demonstrated a persistent deficiency of both proteins, excluding a potential effect of disease activity. In conclusion, reduced expression of RIalpha and RIbeta transcripts is associated with a decrement in RIalpha and RIbeta proteins and may contribute to deficient type I protein kinase A isozyme activity in SLE T cells.  (+info)

Structural characterization of the membrane-associated regulatory subunit of type I cAMP-dependent protein kinase by mass spectrometry: identification of Ser81 as the in vivo phosphorylation site of RIalpha. (3/164)

The mechanism by which the type Ialpha regulatory subunit (RIalpha) of cAMP-dependent protein kinase is localized to cell membranes is unknown. To determine if structural modification of RIalpha is important for membrane association, both beef skeletal muscle cytosolic RI and beef heart membrane-associated RI were characterized by electrospray ionization mass spectrometry. Total sequence coverage was 98% for both the membrane-associated and cytosolic forms of RI after digestion with AspN protease or trypsin. Sequence data indicated that membrane-associated and cytosolic forms of RI were the same RIalpha gene product. A single RIalpha phosphorylation site was identified at Ser81 located near the autoinhibitory domain of both membrane-associated and cytosolic RIalpha. Because both R subunit preparations were 30-40% phosphorylated, this post-translational modification could not be responsible for the membrane compartmentation of the majority of RIalpha. Mass spectrometry also indicated that membrane-associated RIalpha had a higher extent of disulfide bond formation in the amino-terminal dimerization domain. No other structural differences between cytosolic and membrane-associated RIalpha were detected. Consistent with these data, masses of the intact proteins were identical by LCQ mass spectrometry. Lack of detectable structural differences between membrane-associated and cytosolic RIalpha strongly suggests an interaction between RIalpha and anchoring proteins or membrane lipids as more likely mechanisms for explaining RIalpha membrane association in the heart.  (+info)

Protein kinase A-Ialpha subunit-directed antisense inhibition of ovarian cancer cell growth: crosstalk with tyrosine kinase signaling pathway. (4/164)

Expression of the RIalpha subunit of cAMP-dependent protein kinase type I is increased in human cancers in which an autocrine pathway for epidermal growth factor-related growth factors is activated. We have investigated the effect of sequence-specific inhibition of RIalpha gene expression on ovarian cancer cell growth. We report that RIalpha antisense treatment results in a reduction in RIalpha expression and protein kinase A type I, and inhibition of cell growth. The growth inhibition was accompanied by changes in cell morphology and appearance of apoptotic nuclei. In addition, EGF receptor, c-erbB-2 and c-erbB-3 levels were reduced, and the basal and EGF-stimulated mitogen-activated protein kinase activities were reduced. Protein kinase A type I and EGF receptor levels were also reduced in cells overexpressing EGF receptor antisense cDNA. These results suggest that the antisense depletion of RIalpha leads to blockade of both the serine-threonine kinase and the tyrosine kinase signaling pathways resulting in arrest of ovarian cancer cell growth.  (+info)

Antitumor activity and pharmacokinetics of a mixed-backbone antisense oligonucleotide targeted to the RIalpha subunit of protein kinase A after oral administration. (5/164)

Overexpression of the RIalpha subunit of cAMP-dependent protein kinase (PKA) has been demonstrated in various human cancers. PKA has been suggested as a potential target for cancer therapy. The goal of the present study was to evaluate an anti-PKA antisense oligonucleotide (mixed-backbone oligonucleotide) as a therapeutic approach to human cancer treatment. The identified oligonucleotide inhibited the growth of cell lines of human colon cancer (LS174T, DLD-1), leukemia (HL-60), breast cancer (MCF-7, MDA-MB-468), and lung cancer (A549) in a time-, concentration-, and sequence-dependent manner. In a dose-dependent manner, the oligonucleotide displayed in vivo antitumor activity in severe combined immunodeficient and nude mice bearing xenografts of human cancers of the colon (LS174T), breast (MDA-MB-468), and lung (A549). The routes of drug administration were intraperitoneal and oral. Synergistic effects were found when the antisense oligonucleotide was used in combination with the cancer chemotherapeutic agent cisplatin. The pharmacokinetics of the oligonucleotide after oral administration of (35)S-labeled oligonucleotide into tumor-bearing mice indicated an accumulation and retention of the oligonucleotide in tumor tissue. This study further provides a basis for clinical studies of the antisense oligonucleotide targeted to the RIalpha subunit of PKA (GEM 231) as a cancer therapeutic agent used alone or in combination with conventional chemotherapy.  (+info)

A safety and pharmacokinetic study of a mixed-backbone oligonucleotide (GEM231) targeting the type I protein kinase A by two-hour infusions in patients with refractory solid tumors. (6/164)

GEM231 is a mixed-backbone oligonucleotide targeting the regulatory subunit alpha of type I protein kinase A, which plays an important role in growth and maintenance of malignancies. Preclinically, GEM231 inhibited human cancer xenografts either alone or synergistically with chemotherapeutic agents and has demonstrated an improved metabolic stability and safety profile compared to the first-generation compounds. Objectives of this study were to define the safety profile and pharmacokinetics of GEM231 administered as 2-h IV infusions twice weekly in patients with refractory solid tumors. Fourteen patients (13 evaluable for safety) received escalating doses of GEM231 at 20-360 mg/m2 (2.5-9 mg/kg). Tumor histologies included non-small cell lung cancer, renal cell cancer, sarcoma, and others. The plasma pharmacokinetics of GEM231 were linear and predictable. Maximum plasma concentration (Cmax) reached 50-70 microg/ml (8-13 microM) at dose 360 mg/m2 and 27-32 microg/ml at dose 240 mg/m2. The plasma half-life was about 1.5 h. The only clinical toxicities were transient grade I-II fever and fatigue at doses > or = 240 mg/m2. There was no treatment-related complement activation or thrombocytopenia at any dose level, except with the first dose in one patient who had pre-existing borderline thrombocytopenia. Transient activated partial thrombin time prolongation occurred at doses > or =160 mg/m2. Dose-limiting toxicities included transient activated partial thrombin time prolongation (one of three patients at 360 mg/m2) and cumulative reversible transaminase elevation (three of three patients at 360 mg/m2 and three of six patients at 240 mg/m2 during weeks 3-10). One patient with colon cancer had stabilization of a previously rising carcinoembryonic antigen. Thus, in this first clinical evaluation of a mixed-backbone oligonucleotide in cancer patients, high plasma concentrations of GEM231 were well tolerated without significant acute toxicities, but prolonged treatment was associated with reversible transaminitis. Although 240 mg/m2 by 2-h infusion twice weekly was safe for a 4-week treatment duration, alternative dosing schedules are being tested to minimize the cumulative toxicity, which will be essential to extend the duration of therapy at the highest GEM231 dose tested.  (+info)

8-chloro-cAMP inhibits smooth muscle cell proliferation in vitro and neointima formation induced by balloon injury in vivo. (7/164)

OBJECTIVES: The aims of the present study were to assess 1) the effect of 8-C1-cAMP (cyclic-3'-5'-adenosine monophosphate) on vascular smooth muscle cell (VSMC) proliferation in vitro and 2) the efficacy of systemic administration of 8-C1-cAMP on neointimal formation after balloon injury in vivo. BACKGROUND: Neointimal formation after vascular injury is responsible for restenosis after arterial stenting. Recently, 8-C1-cAMP, a cAMP analogue that induces growth arrest, has been safely administered in phase I studies in humans. METHODS: The effect of 8-C1-cAMP on cell proliferation was first assessed on SMCs in vitro. To study the effects of cAMP in vivo, balloon injury was performed in 67 rats using a 2F Fogarty balloon catheter. RESULTS: The 8-C1-cAMP markedly inhibited VSMC proliferation in vitro, reduced protein kinase A (PKA) RIalpha subunit expression, and induced PKA RIIbeta subunit expression. In addition, 8-C1-cAMP reduced, in a dose-dependent manner, neointimal area and neointima/media ratio after balloon injury. The proliferative activity, assessed by proliferating nuclear cell antigen immunostaining, revealed a reduction of proliferative activity of VSMCs in vivo in the 8-C1-cAMP group. Moreover, the systemic administration of 8-C1-cAMP did not affect renal function, blood pressure and heart rate. CONCLUSIONS: We conclude that 8-C1-cAMP potently inhibits VSMC proliferation in vitro and reduces neointima formation by balloon injury in vivo after systemic administration. These data may have a clinical relevance in designing future strategies to prevent restenosis after arterial stenting and perhaps after percutaneous transluminal coronary angioplasty.  (+info)

Alternative 5'-exons of the mouse cAMP-dependent protein kinase subunit RIalpha gene are conserved and expressed in both a ubiquitous and tissue-restricted fashion. (8/164)

The activity of cAMP-dependent protein kinase is controlled by its regulatory subunits. Mouse RIalpha regulatory subunit expression is initiated from five different non-coding 5'-regions (exons 1a, 1b, 1c, 1d and 1e). This organization appears to be conserved among species. All mouse tissues accumulate exon 1a and 1b transcripts and most contain more 1b than 1a, except brain, heart and oesophagus. Exon 1d and 1e transcripts are found in several tissues, while exon 1c is testis-specific. All five transcripts are in RIalpha-rich tissues: gonads and adrenal glands.  (+info)

We report two interesting cases of CS in a pair of adolescent age-group brothers, due to ACTH-independent PPNAD, as a part of the CC. PPNAD is the most common cause of CS in the adolescent age group, with > 50% of the cases having CC, characterised by a mutation in PRKAR1A (protein kinase type 1-alpha regulatory subunit) [2]. Although genetic testing could not be done, both the patients fulfilled the clinical criteria for CC; the two major criteria which were satisfied were - the presence of spotty skin pigmentation, and PPNAD, while the presence of positive family history in a first-degree relative fulfilled the supplemental criteria [3]. Both the cases exhibited certain peculiarities typical of PPNAD, while few features were atypical. Both of them had a florid clinical presentation with severe stunting and various features of protein catabolism, whereas PPNAD is usually associated with a milder presentation. This could probably be attributed to the long duration of the cortisol burden in both ...
PRKAR2A_ENST00000296446 Gene, Drug Resistance, Tissue Distribution, Mutation Distribution, Variants, PRKAR2A_ENST00000296446 Genome Browser, PRKAR2A_ENST00000296446 References
Plasmid pDONR223-PRKAR1B from Dr. William Hahns lab contains the insert PRKAR1B and is published in Nature. 2010 Nov 24. ():. This plasmid is available through Addgene.
For many industries, CNC machined parts are a common requirement for their manufacturing process. Runsom Precision Co.,Ltd is well known in the industry for their high precision CNC machining capabilities for the mass production of small components required for manufacturing various products. The company ensures a speedy delivery of these CNC machined parts for industries to continue their manufacturing process without any hindrance.. According to the company spokesperson, they can supply CNC machining parts within 48 hours of receiving orders from the client. With their advanced machining equipment and a streamlined machining process, they have the ability to produce CNC machining components in bulk for their industrial clients. The company also enjoys a well-established supply chain network to ensure a speedy delivery of the processed machining parts to their clients in different parts of the world.. The spokesperson reveals that they offer an impeccable CNC machining service to supply ...
Sara Carmo Silva, Clévio Nóbrega, Marisa Ferreira-Marques, Mariana Botelho, Célia A. Aveleira, Cláudia Cavadas (Neuroendrocrinology and Aging Group, CNC) and Luís Pereira de Almeida (Vectos and Gene Therapy, CNC) in collaboration with Clévio Nóbrega (CBMR - Centre for Bio-Medical Research, UAlg ...
Designed for use with small to mid-sized automated cutting machines, this versatile, easy-to-use CNC offers advanced capabilities across a wide range of applications.
Primary pigmented nodular adrenocortical disease is a rare cause of adrenocorticotropic hormone-independent Cushings syndrome. We report an uncommon primary pigmented nodular adrenocortical disease case presenting with a unilateral adrenocortical nodule and provide a brief overview of the existing literature. A 27-year-old Caucasian woman was admitted to our Department with adrenocorticotropic hormone-independent Cushings syndrome. Its cause was initially considered a left adrenocortical adenoma based on computer tomography imaging. The patient underwent left laparoscopic adrenalectomy and histological examination revealed pigmented micronodular adrenal hyperplasia. Evaluation for the presence of Carney complex was negative. Six months later recurrence of hypercortisolism was documented and a right laparoscopic adrenalectomy was performed further establishing the diagnosis of primary pigmented nodular adrenocortical disease. After a nine-year follow-up there is no evidence of residual disease. Even
Primary pigmented nodular adrenocortical disease (PPNAD) is a pituitary-independent, primary adrenal form of hypercortisolism characterized by (a) resistance to suppression by dexamethasone and abolition of the normal diurnal rhythm of cortisol secretion, and (b) distinctive, bilateral, histopathologic changes of the adrenal glands, such as the formation of variably sized, pigmented nodular adenomas, loss of normal zonation and atrophy of the extranodular cortex. PPNAD can be associated with a variety of other manifestations, such as myxomas of the skin, heart, breast and other sites, psammomatous melanotic swannomas involving the peripheral nervous system (PNS), lentigines and blue nevi of the skin and mucosae, growth hormone (GH)-producing adenomas of the pituitary, testicular Sertoli cell tumors, and possibly other neoplasms (adrenocortical and thyroid follicular carcinoma, and ovarian cysts). These associations constitute a distinct clinical syndrome, Carney complex, a genetic syndrome. At ...
Primary pigmented nodular adrenocortical disease (PPNAD) is a pituitary-independent, primary adrenal form of hypercortisolism characterized by (a) resistance to suppression by dexamethasone and abolition of the normal diurnal rhythm of cortisol secretion, and (b) distinctive, bilateral, histopathologic changes of the adrenal glands, such as the formation of variably sized, pigmented nodular adenomas, loss of normal zonation and atrophy of the extranodular cortex. PPNAD can be associated with a variety of other manifestations, such as myxomas of the skin, heart, breast and other sites, psammomatous melanotic swannomas involving the peripheral nervous system (PNS), lentigines and blue nevi of the skin and mucosae, growth hormone (GH)-producing adenomas of the pituitary, testicular Sertoli cell tumors, and possibly other neoplasms (adrenocortical and thyroid follicular carcinoma, and ovarian cysts). These associations constitute a distinct clinical syndrome, Carney complex, a genetic syndrome. At ...
Carney complex (CNC) is a rare multiple neoplasia syndrome characterized by spotty pigmentation of the skin and mucosa in association with various non-endocrine and endocrine tumors, including primary pigmented nodular adrenocortical disease (PPNAD). A 20-year-old woman was referred for suspected Cushing syndrome. She had signs of cortisol excess as well as skin lentigines on physical examination. Biochemical investigation was suggestive of corticotropin (ACTH)-independent Cushing syndrome. Unenhanced computed tomography scan of the abdomen did not reveal an obvious adrenal mass. She subsequently underwent bilateral laparoscopic adrenalectomy, and histopathology was consistent with PPNAD. Genetic testing revealed a novel frameshift pathogenic variant c.488delC/p.Thr163MetfsX2 (ClinVar Variation ID: 424516) in the PRKAR1A gene, consistent with clinical suspicion for CNC. Evaluation for other clinical features of the complex was unrevealing. We present a case of PPNAD-associated Cushing syndrome ...
Carney complex (CNC) is a rare multiple neoplasia syndrome characterized by spotty pigmentation of the skin and mucosa in association with various non-endocrine and endocrine tumors, including primary pigmented nodular adrenocortical disease (PPNAD). A 20-year-old woman was referred for suspected Cushing syndrome. She had signs of cortisol excess as well as skin lentigines on physical examination. Biochemical investigation was suggestive of corticotropin (ACTH)-independent Cushing syndrome. Unenhanced computed tomography scan of the abdomen did not reveal an obvious adrenal mass. She subsequently underwent bilateral laparoscopic adrenalectomy, and histopathology was consistent with PPNAD. Genetic testing revealed a novel frameshift pathogenic variant c.488delC/p.Thr163MetfsX2 (ClinVar Variation ID: 424516) in the PRKAR1A gene, consistent with clinical suspicion for CNC. Evaluation for other clinical features of the complex was unrevealing. We present a case of PPNAD-associated Cushing syndrome ...
Genetic variants in components of the protein kinase A (PKA) enzyme have been associated with various defects and neoplasms in the context of Carney complex (CNC) and in isolated cases, such as in primary pigmented nodular adrenocortical disease (PPNAD), cortisol-producing adrenal adenomas (CPAs), and various cancers. PRKAR1A mutations have been found in subjects with impaired cAMP-dependent signaling and skeletal defects; bone tumors also develop in both humans and mice with PKA abnormalities. We studied the PRKACB gene in 148 subjects with PPNAD and related disorders, who did not have other PKA-related defects and identified two subjects with possibly pathogenic PRKACB gene variants and unusual bone and endocrine phenotypes. The first presented with bone and other abnormalities and carried a de novo c.858_860GAA (p.K286del) variant. The second subject carried the c.899C,T (p.T300M or p.T347M in another isoform) variant and had a PPNAD-like phenotype. Both variants are highly conserved in the ...
specificalPrinciple of the assay: PRKAR1A ELISA kit applies the competitive enzyme immunoassay technique utilizing a monoclonal anti-PRKAR1A antibody and an PRKAR1A-HRP conjugate. The assay sample and buffer are incubated together with PRKAR1A-HRP conjugate in pre-coated plate for one hour. After the incubation period, the wells are decanted and washed five times. The wells are then incubated with a substrate for HRP enzyme. The product of the enzyme-substrate reaction forms a blue colored complex. Finally, a stop solution is added to stop the reaction, which will then turn the solution yellow. The intensity of color is measured spectrophotometrically at 450nm in a microplate reader. The intensity of the color is inversely proportional to the PRKAR1A concentration since PRKAR1A from samples and PRKAR1A-HRP conjugate compete for the anti-PRKAR1A antibody binding site. Since the number of sites is limited, as more sites are occupied by PRKAR1A from the sample, fewer sites are left to bind ...
Antisens Protein of HTLV-2 (APH-2) was described in 2009. APH-2 mRNA is expressed in vivo in most HTLV-2 carriers. In recent years, several laboratories have searched for similarities and/or differences between APH-2 and the antisens protein of HTLV-1, HBZ. Similarly to HBZ, APH-2 negatively regulates HTLV-2 transcription. However, it does not promote cell proliferation. In vivo, APH-2 localizes in discrete nuclear domains distinct from nucleoli. We therefore characterized APH-2 subcellular localization, in order to decipher the determinants of such localization and to correlate it or not with APH-2 functions. We first identify APH-2-containing nuclear domains as PML nuclear bodies (PML-NB). PML-NB are modulators of a number of cellular processes ranging from transcription regulation to cell proliferation and death. We show that both an in silico-identified nuclear localization signal and the carboxy-terminal LXXLL motif contribute to APH-2 targeting to PML-NB. Covalent modification of APH-2 by ...
Expression of PRKAR2B (PRKAR2) in cancer tissue. The cancer tissue page shows antibody staining of the protein in 20 different cancers.
CNC Routers - CNC Plasma Cutters - CNC Manufacturer - CNC Tooling - CNC Router Machines. Techno CNC Systems sells CNC Routers, CNC Plasma cutters and CNC Equipment. We focus on manufacturing new CNC routers or used CNC router machines for all production types. We manufacture CNC Routers for wood, CNC routers for plastics, CNC routers for metals and CNC routers for cabinetry. We offer affordable and quality CNC routers for woodworking shops, cabinet shops, theatres, general fabrication, sign shops and more.
Tapping the Translation Potential of cAMP-Signalling and Amyloid Inhibition using NMR. Abstract. Our work focuses on the use of NMR spectroscopy to understand two fundamental processes in humans: intracellular cAMP-dependent conformational switches and extracellular amyloid inhibition by plasma proteins. Eukaryotic cAMP-binding domains (CBDs) control multiple cellular functions (e.g. phosphorylation by protein kinase A - PKA, guanine exchange by the exchange protein directly activated by cAMP - EPAC, and ion channel gating in the hyperpolarization and cyclic-nucleotide modulated ion channels - HCN). Hence, the translational potential arising from the manipulation of cAMP-dependent signaling pathways is high. However, the ubiquity of eukaryotic CBDs also poses a challenge in terms of selectivity. Before the full translational potential of cAMP-signalling can be tapped, it is critical to understand the structural basis for selective cAMP agonism and antagonism, which is being deciphered through ...
The spotty skin pigmentation and lentigines occur most commonly on the face, especially on the lips, eyelids, conjunctiva and oral mucosa.[3] Cardiac myxomas may lead to embolic strokes and heart failure[4] and may present with fever, joint pain, shortness of breath, diastolic rumble and tumor plop. Myxomas may also occur outside the heart, usually in the skin and breast. Endocrine tumors may manifest as disorders such as Cushing syndrome. The most common endocrine gland manifestation is an ACTH-independent Cushings syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). The LAMB acronym refers to lentigines, atrial myxomas, and blue nevi.[1] NAME refers to nevi, atrial myxoma, myxoid neurofibromas, and ephelides.[1] Testicular cancer, particularly Sertoli cell type, is associated with Carney syndrome.[5] Thyroid and pancreas cancer may also occur.[6][7] Although J Aidan Carney also described Carneys triad it is entirely different.[8] ...
TY - JOUR. T1 - Operative management of Cushing Syndrome secondary to micronodular adrenal hyperplasia. AU - Powell, Anathea C.. AU - Stratakis, Constantine A.. AU - Patronas, Nicholas J.. AU - Steinberg, Seth M.. AU - Batista, Dalia. AU - Alexander, H. Richard. AU - Pingpank, James F.. AU - Keil, Meg. AU - Bartlett, David L.. AU - Libutti, Steven K.. PY - 2008/6/1. Y1 - 2008/6/1. N2 - Background: We reviewed our experience with micronodular adrenal hyperplasia (MAH), its pigmented variant primary pigmented nodular adrenocortical disease (PPNAD), and the association with Carneys complex (CNC) to better characterize these disorders. Methods: This retrospective study analyzes clinical data and operative reports of 34 patients identified with MAH and/or PPNAD who underwent resection between 1969 and 2006 at the Clinical Research Center, an inpatient research hospital at the National Institutes of Health. Symptoms and anthropometric and biochemical data were used to evaluate effect of resection. ...
Introduction: We present a rare variety of adrenocorticotrophic hormone (ACTH)-independent Cushings syndrome known as primary pigmented nodular adrenocortical disease (PPNAD). Clinical Picture: The patient initially underwent unilateral adrenalectomy for what was thought to be a left adrenal adenoma. Outcome: Partial resolution of symptoms and demonstrable persistent hypercortisolism after surgery prompted further evaluation with findings leading to the diagnosis of Carney complex. A review of the adrenal histology was consistent with PPNAD. Conclusion: This entity of PPNAD, which has rarely been reported in Asians, forms part of the Carney complex. The diagnosis may not be simple and straightforward, as illustrated in this patient ...
Pituitary tumours occur with increased frequency among patients with CNC.8PRKAR1A, the gene mutated in almost half of the patients with CNC,1,2 codes for the most abundant regulatory subunit of cAMP dependent PKA, a cellular system highly involved in pituitary cell growth and function.13,15,16 In the present study, we investigated the hypothesis that LOH or alterations of PRKAR1As sequence are involved in sporadic pituitary tumours, as well as inherited, non-CNC related pituitary tumours. The results of the experiments described here suggested that the RI-α subunit of PKA is not a significant contributor to tumorigenesis in pituitary cells, as shown by infrequent LOH of the PRKAR1A 17q22-24 locus and lack of PRKAR1A mutations in a large international series of pituitary tumours. Although the number of families that was investigated was small, we may also conclude from this study that PRKAR1A mutations are not responsible for a significant number of non-CNC related inherited pituitary lesions. ...
Learn more about Adrenocortical Disease in ferrets in this informative article from The Center for Bird and Exotic Medicine in Bothell, WA.
Background: Histiocytic sarcoma (HS) is an aggressive hematological neoplasm that responds poorly to therapy. The molecular etiology and pathology of this disease remain unclear, hampering the development of an effective therapy. Therefore, a need for more, and more realistic, animal models remains. Lymphoproliferative disorders have been reported in mice deficient for the prkar1a gene coding for the regulatory subunit type 1A of protein kinase A (PKA), but nothing is known about the role of type II PKA regulatory subunits in hematologic malignancies.. Methods: Mice deficient for the Prkar1a and Prkar2a alleles were previously reported (Kirschner et al, 2005 και Burton et al, 1997) and were kept on a mixed genetic background (C57BL/129Sv). Mice were crossed to create prkar2a+/- and prkar2a-/-. Mice were phenotyped at the ages of 3-6-9-12-18 months or when they exhibited signs of advanced disease. Tissues were collected for histological and molecular analysis.. Results: Unexpectedly, mice ...
Rabbit polyclonal antibody raised against a full-length human PRKAR1B protein. PRKAR1B (NP_002726.1, 1 a.a. ~ 381 a.a) full-length human protein. (H00005575-D01P) - Products - Abnova
Reactome is pathway database which provides intuitive bioinformatics tools for the visualisation, interpretation and analysis of pathway knowledge.
There is no cure for acrodysostosis. Treatment of the condition will be based on the symptoms that are present. Physical therapy may be helpful to treat mobility or movement problems. Jaw problems or disorders may be treated with orthodontic supports. Braces can be used to correct misaligned teeth. Surgery may be recommended in some cases for correcting bone or jaw problems.. Children with mental retardation or learning disabilities may benefit from services that help them to reach their full potential. Services can include:. ...
PIK3C2B (phosphatidylinositol-4-phosphate 3-kinase catalytic subunit type 2 beta), Authors: Dessen P. Published in: Atlas Genet Cytogenet Oncol Haematol.
View Notes - Bacterial Recombination from MCB 2000 at University of Florida. BACTERIAL RECOMBINATION Purposes A. Vaccine production (subunit type) B. Production of proteins (growth hormone) C.
The worlds first wiki where authorship really matters. Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts.
DGIdb, The Drug Gene Interaction Database, is a research resource that can be used to search candidate genes or drugs against the known and potentially druggable genome.
CNC Cutting Machine For Angle Bar CNC cutting machine for angle bar is used for notching corner of angle steel in the angle tower industry The notching die is rectangular double edge blade with multi directional rotary Only to adjust the rotating die to do the notching work so that it is not need to change ...
This course will cover basic programming techniques, setup, operation and maintenance of CNC woodworking routers. Basic manual code creation, controller manipulation, maintenance, tooling, machine orientation and hands on part manufacturing will be presented. Specific parts will be programmed and machined.
高い抗原親和性、特異性と安定した品質を兼ね備えたアブカムのウサギ・モノクローナル抗体 RabMAb® ab75993 交差種: Ms,Rat,Hu 適用: WB,IP,IHC-P,Flow Cyt,ICC/IF
Carney complex and its subsets LAMB syndrome and NAME syndrome are autosomal dominant conditions comprising myxomas of the heart and skin, hyperpigmentation of the skin (lentiginosis), and endocrine overactivity. It is distinct from Carneys triad. Approximately 7% of all cardiac myxomas are associated with Carney complex. The spotty skin pigmentation and lentigines occur most commonly on the face, especially on the lips, eyelids, conjunctiva and oral mucosa. Cardiac myxomas may lead to embolic strokes and heart failure and may present with fever, joint pain, shortness of breath, diastolic rumble and tumor plop. Myxomas may also occur outside the heart, usually in the skin and breast. Endocrine tumors may manifest as disorders such as Cushing syndrome. The most common endocrine gland manifestation is an ACTH-independent Cushings syndrome due to primary pigmented nodular adrenocortical disease (PPNAD). The LAMB acronym refers to lentigines, atrial myxomas, and blue nevi. NAME refers to nevi, ...
A 60 year-old male was referred for treatment of a cardiac myxoma in the right atrium. He had a past history of left atrial cardiac myxoma at age 49 and pituitary microadenoma related to acromegaly at age 55. He did not have a family history of cardiac neoplasm or endocrinopathy. The intracardiac tumor was resected and its pathology was compatible with myxoma. A diagnosis of Carney complex (CNC) was made because the diagnostic criteria of this neoplastic syndrome were satisfied by the presence of recurrent cardiac myxoma, endocrine tumor and spotty skin pigmentation. In genetic analysis novel frame shift mutation was detected in exon 2 in a heterozygous fashion in the causative gene of CNC, protein kinase A regulatory subunit 1 α (PRKAR1A). This genetic mutation is thought to cause haplo-insufficiency of PRKAR1A resulting in tumorigenesis. Although it is the most common, usually benign, cardiac tumor, myxoma can cause a critical clinical situation and thus detecting the PRKAR1A mutation can ...
Assessment of cytologic evaluation of preputial epithelial cells as a diagnostic test for detection of adrenocortical disease in castrated ferrets
London E, Nesterova M, Sinaii N, Szarek E, Chanturiya T, Mastroyannis SA, Gavrilova O, Stratakis CA: Differentially regulated protein kinase A (PKA) activity in adipose tissue and liver is associated with resistance to diet-induced obesity and glucose intolerance in mice that lack PKA regulatory subunit type IIα. Endocrinology; 2014 Sep;155(9):3397-408 ...
London E, Nesterova M, Sinaii N, Szarek E, Chanturiya T, Mastroyannis SA, Gavrilova O, Stratakis CA: Differentially regulated protein kinase A (PKA) activity in adipose tissue and liver is associated with resistance to diet-induced obesity and glucose intolerance in mice that lack PKA regulatory subunit type IIα. Endocrinology; 2014 Sep;155(9):3397-408 ...
Most PRKAR1A tumorigenic mutations lead to nonsense mRNA that is decayed; tumor formation has been associated with an increase in type II protein kinase A (PKA) subunits. The IVS6+1G>T PRKAR1A mutation leads to a protein lacking exon 6 sequences [R1 alpha Delta 184-236 (R1 alpha Delta 6)]. We compared in vitro R1 alpha Delta 6 with wild-type (wt) R1 alpha. We assessed PKA activity and subunit expression, phosphorylation of target molecules, and properties of wt-R1 alpha and mutant (mt) R1 alpha; we observed by confocal microscopy R1 alpha tagged with green fluorescent protein and its interactions with Cerulean-tagged catalytic subunit (C alpha). Introduction of the R1 alpha Delta 6 led to aberrant cellular morphology and higher PKA activity but no increase in type II PKA subunits. There was diffuse, cytoplasmic localization of R1 alpha protein in wt-R1 alpha- and R1 alpha Delta 6-transfected cells but the former also exhibited discrete aggregates of R1 alpha that bound C alpha; these were absent ...
CNC Plastic Parts CNC Machining Product Made in China, Find details about China Machining, CNC Machining from CNC Plastic Parts CNC Machining Product Made in China - Holy Precision Manufacturing Co., Limited
China Customized 2D & 3D Rotary CNC Router Machine, Find details about China CNC Router, CNC Router Machine from Customized 2D & 3D Rotary CNC Router Machine - Jinan Guanjiahong CNC Machinery Co., Ltd.
Jinan Tenma Machinery Co., Ltd. production following CNC Router:Woodworking CNC Router,Marble CNC Router,Advertising CNC Router,EPS CNC Router,CNC Machining Center,etc.
China Bakelite/Phenol-Formaldehyde CNC Machining Part for Automation Machinery, Find details about China Phenol-Formaldehyde CNC Machining, Bakelite CNC Machining from Bakelite/Phenol-Formaldehyde CNC Machining Part for Automation Machinery - Changzhou KYLT Import & Export Co., Ltd.
Sargent Metal Fabrication is an industrial supplier of bearings, bp, cnc lathes, cnc mills, cnc turning, cob, grinders, knee mills, lathes, machined.
China High Precise CNC Machined & Turned Parts-OEM Metal Parts, Find details about China Machining, CNC Machining from High Precise CNC Machined & Turned Parts-OEM Metal Parts - Holy Precision Manufacturing Co., Limited
Improve your product manufacturability for CNC punching with Falcon Precisions design tips. Falcon Precision have over 25 years experience of CNC punching.
Hardinge | Gosiger provides the CNC Machine Tools industry with products and knowledge on 5-axis, VMC, HMC, CNC machining centers, lathes, grinders, and more.
What should you look for to see if your CNC plasma cutting machines consumables are worn? Find out how to tell in this post from Multicam.
Homag Group is exhibiting the product CNC Manufacturing cells at LIGNA from 22 to 26 May. 2017 in Hannover, Germany. Plan your visit to the trade fair and search for further products.
Kúpte použité STEMAC 315 CNC Plasma Cutting Machine od 7370 € ✅ Rok výroby: 2018 ✅ Poloha: IT ✅ Dražte teraz ➤ Surplex.com
A single-light, oval backed wall sconce of cast and tooled brass. Fitted with a satin clear glass trumpet shade. Shown in Silverplate.
... sequence formed by the fusion of ret tyrosine kinase and the regulatory subunit RI alpha of cyclic AMP-dependent protein kinase ... "A kinase anchoring protein (AKAP) interaction and dimerization of the RIalpha and RIbeta regulatory subunits of protein kinase ... Guild BC, Strominger JL (1984). "HLA-A2 antigen phosphorylation in vitro by cyclic AMP-dependent protein kinase. Sites of ... cAMP-dependent protein kinase type I-alpha regulatory subunit is an enzyme that in humans is encoded by the PRKAR1A gene. cAMP ...
... or cyclic AMP-dependent protein kinase. 1992: Elected to the American Academy of Arts and Sciences 1996: Elected to the ... RIalpha) subunits of PKA". Science. 307 (5710): 690-6. doi:10.1126/science.1104607. PMID 15692043. Zhang, P; Smith-Nguyen, EV; ... "Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase". Science. 253 (5018): ... She is known for her research on protein kinases, particularly protein kinase A. She was elected to the Institute of Medicine ...
... such as the cyclic adenosine monophosphate (cAMP) pathway. cAMP activates cAMP-dependent protein kinase A (PKA) either to ... Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit * Cyclic AMP-Dependent Protein Kinase RIalpha Subunit ... Cyclic AMP-Dependent Protein Kinase RIIbeta Subunit * Cyclic AMP-Dependent Protein Kinase RIalpha Subunit ... such as the cyclic adenosine monophosphate (cAMP) pathway. cAMP activates cAMP-dependent protein kinase A (PKA) either to ...
... subunits and a regulatory (R) subunit dimer (R(2)C(2)). The kinase is activated by the binding of cAMPs to the two cyclic ... nucleotide binding domains (CBDs), A and B, on each R-subunit. Despite extensive study, details of the allosteric … ... Protein kinase A (PKA) holoenzyme consists of two catalytic (C) ... Cyclic AMP-Dependent Protein Kinase RIalpha Subunit * Mutant ... Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / chemistry * Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / ...
Prkar1a = cyclic AMP-dependent protein kinase RIalpha subunit; Prkaca = cyclic AMP-dependent protein kinase catalytic subunit) ... protein kinase C delta type , protein kinase-delta2 , protein kinase C, delta , protein kinase C delta type-like , protein ... protein kinase C, delta V , protein kinase C[d] , protein kinase C delta , PKA C-alpha , cAMP-dependent protein kinase ... Protein Kinase, AMP-Activated, alpha 1 Catalytic Subunit ELISA Kits * Protein Kinase, AMP-Activated, alpha 2 Catalytic Subunit ...
Prkar1a = cyclic AMP-dependent protein kinase RIalpha subunit; Prkaca = cyclic AMP-dependent protein kinase catalytic subunit) ... cAMP-dependent protein kinase catalytic subunit alpha , sperm cAMP-dependent protein kinase catalytic subunit , protein kinase ... protein kinase C, delta IV , protein kinase C, delta V , protein kinase C[d] , protein kinase-delta2 , protein kinase C, delta ... protein kinase C delta VIII , protein kinase C delta type , tyrosine-protein kinase PRKCD , nPKC-delta , protein kinase C delta ...
Cyclic AMP-Dependent Protein Kinase RIalpha Subunit/chemistry*/genetics/metabolism. *Models, Molecular* ... Cyclic AMP-Dependent Protein Kinase Catalytic Subunits/chemistry*/genetics/metabolism. *Cyclic AMP-Dependent Protein Kinase ... Cyclic AMP-Dependent Protein Kinase Catalytic Subunits/chemistry*/genetics/metabolism. * ... Protein Kinase A (PKA) is the major receptor for the cyclic adenosine monophosphate (cAMP) secondary messenger in eukaryotes. ...
... sequence formed by the fusion of ret tyrosine kinase and the regulatory subunit RI alpha of cyclic AMP-dependent protein kinase ... sequence formed by the fusion of ret tyrosine kinase and the regulatory subunit RI alpha of cyclic AMP-dependent protein kinase ... sequence formed by the fusion of ret tyrosine kinase and the regulatory subunit RI alpha of cyclic AMP-dependent protein kinase ... sequence formed by the fusion of ret tyrosine kinase and the regulatory subunit RI alpha of cyclic AMP-dependent protein kinase ...
Solberg, Rigmor & Jahnsen, Tore (1994). Human type I regulatory subunits of cyclic AMP-dependent protein kinases. Structure, ... Two promoters in the RIalpha gene of cyclic AMP-dependent protein kinase provide means of differential regulation. ... Cyclic AMP-dependent protein kinase (vertebrates), In G. Hardie & S. Hanks (ed.), The Protein Kinase FactsBook. Elsevier. ISBN ... and regulation of cyclic AMP-dependent protein kinases. * Skålhegg, Bjørn Steen & Jahnsen, Tore (1993). Isozymes of cyclic AMP- ...
Cyclic AMP (cAMP) and cAMP-dependent protein kinase (PKA) are critical regulators of neuronal differentiation. The expression, ... consisting of the regulatory subunit RIalpha and the catalytic subunit Calpha. Low levels of PKA type II consisting of RIIalpha ... Hansson, Vidar; Skålhegg, Bjørn Steen & Tasken, Kjetil (1999). Cyclic-AMP-dependent protein kinase (PKA) in testicular cells. ... LH and FSH regulate via cyclic adenosine 35 cyclic monophosphate (cAMP) and cAMP-dependent protein kinase (PKA), steroid ...
Cyclic AMP regulates expression of the RI alpha subunit of cAMP-dependent protein kinase through an alternatively spliced 5 ... Reciprocal regulation of mRNA and protein for subunits of cAMP-dependent protein kinase (RI alpha and C alpha) by cAMP in a ... Mechanisms of FOXC2- and FOXD1-mediated regulation of the RI alpha subunit of cAMP-dependent protein kinase include release of ... The alpha-subunit mRNAs for Gs and Go2 are differentially regulated by protein kinase A and protein kinase C in rat Sertoli ...
8. ReadLK, MikkelsenRB (1990) Cyclic AMP- and Ca2+ -dependent protein kinases in Plasmodium falciparum. Exp Parasitol 71: 39-48 ... 7. KimC, XuongNH, TaylorSS (2005) Crystal structure of a complex between the catalytic and regulatory (RIalpha) subunits of PKA ... subunit of the type I cAMP-dependent protein kinase as an inhibitor and substrate of the cGMP-dependent protein kinase. J Biol ... Exchange protein activated by AMP (Epac) mediates cAMP-dependent but protein kinase A-insensitive modulation of vascular ATP- ...
Cyclic AMP-dependent protein kinase is tethered to protein kinase A anchoring proteins (AKAPs) through regulatory subunits (R) ... Dissecting cAMP binding domain A in the RIalpha subunit of cAMP-dependent protein kinase. Distinct subsites for recognition of ... of the cyclic AMP-dependent protein kinase (cAPK), the heat-stable protein kinase inhibitors (PKIs) and the regulatory (R) ... A-kinase anchoring proteins (AKAPs) bind to the regulatory subunit of cAMP-dependent protein kinase (PKA) to direct the kinase ...
... sequence formed by the fusion of ret tyrosine kinase and the regulatory subunit RI alpha of cyclic AMP-dependent protein kinase ... "A kinase anchoring protein (AKAP) interaction and dimerization of the RIalpha and RIbeta regulatory subunits of protein kinase ... Guild BC, Strominger JL (1984). "HLA-A2 antigen phosphorylation in vitro by cyclic AMP-dependent protein kinase. Sites of ... cAMP-dependent protein kinase type I-alpha regulatory subunit is an enzyme that in humans is encoded by the PRKAR1A gene. cAMP ...
Cyclic AMP-Dependent Protein Kinase RIalpha Subunit. Cyclic AMP-Dependent Protein Kinases. Humans. Male. Middle Aged ... Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; 0 / PRKAR1A protein, human; 0 / Proteins; EC 2.7.11.11 / Cyclic AMP- ... Cyclin-Dependent Kinase Inhibitor p27 / metabolism. Female. Follow-Up Studies. Humans. In Situ Hybridization. Ki-67 Antigen / ... Neoplasm Proteins / genetics. Neoplasm Proteins / metabolism. *MedlinePlus Health Information. consumer health - Adrenal Gland ...
RI{alpha}) Subunits of Cyclic AMP-dependent Protein Kinase. Mol Cell Proteomics. 9, 2225-2237 [PMC free article] [PubMed] ... The regulatory (R) subunit of protein kinase A serves to modulate the activity of protein kinase A in a cAMP-dependent manner ... one of the principal targets of cAMP is the cAMP-dependent protein kinase, protein kinase A (PKA), whose regulatory subunit (R- ... 7. Huang L. J., Taylor S. S. (1998) Dissecting cAMP binding domain A in the RIalpha subunit of cAMP-dependent protein kinase. ...
Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; 0 / Neuropeptides; 0 / Prkar1a protein, mouse; 0 / Rac1 protein, mouse; EC ... MeSH-major] Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / physiology. Genes, Neurofibromatosis 2. Neurilemmoma / ... which encodes the type 1A regulatory subunit of protein kinase A.. * To assess the requirement for Rac1 in schwannoma formation ... rac1 GTP-Binding Protein. *PhosphoSitePlus. gene/protein/disease-specific - PhosphoSitePlus® - comprehensive post-translational ...
Cyclic AMP-Dependent Protein Kinase RIalpha Subunit. 1. + +. 195. Dactinomycin. 1. + +. 196. Saposins. 1. + +. ... DNA-Binding Proteins. 1. + +. We do not evaluate or guarantee the accuracy of any content in this site. Click here for the full ...
Cyclic AMP-Dependent Protein Kinase RIalpha Subunit Local Neoplasm Recurrences Multiple Primary Neoplasms ...
Cyclic AMP-Dependent Protein Kinase RIalpha Subunit; 0 / Prkar1a protein, mouse; 0 / Proteins; E0399OZS9N / Cyclic AMP ... Cyclic AMP-Dependent Protein Kinase RIalpha Subunit. Female. Genes, Tumor Suppressor. Genetic Predisposition to Disease. Male. ... Cyclic AMP / physiology. Disease Models, Animal. Multiple Endocrine Neoplasia / genetics. Neurilemmoma / genetics. Proteins / ... A mouse model for the Carney complex tumor syndrome develops neoplasia in cyclic AMP-responsive tissues. Cancer Res; 2005 Jun 1 ...
Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / genetics* Actions. * Search in PubMed ... caused mostly by inactivating mutations of the regulatory subunit 1A of the protein kinase A (PRKAR1A). Primary pigmented ... Germline, protein-truncating mutations of phosphodiesterase type 11A (PDE11A) have been described to predispose to a variety of ... PRKAR1A and PDE11A silencing increase PKA-dependent transcription at baseline and after forskolin stimulation.… ...
Cyclic AMP-Dependent Protein Kinase RIalpha Subunit / genetics* Actions. * Search in PubMed ... Mutations in regulatory subunit type 1A of cyclic adenosine 5-monophosphate-dependent protein kinase (PRKAR1A): phenotype ... Mutations in regulatory subunit type 1A of cyclic adenosine 5-monophosphate-dependent protein kinase (PRKAR1A): phenotype ... is caused by inactivating mutations of the regulatory subunit type 1A of the cAMP-dependent protein kinase (PRKAR1A) gene and ...
cyclic amp-dependent protein kinase rialpha subunit (6) 6 Filter by. Remove filter. cyclic amp-dependent protein kinase rialpha ... Cyclic AMP-Dependent Protein Kinases - genetics , Proteins - metabolism , Base Sequence , Cyclic AMP-Dependent Protein Kinase ... TOR Serine-Threonine Kinases , HeLa Cells , Mutation , Cyclic AMP-Dependent Protein Kinases - deficiency , Fibroblasts - ... The human PRKAR1A gene encodes the regulatory subunit 1-alpha (RI alpha) of the cAMP-dependent protein kinase A (PKA) ...
MAP Kinase Kinase Kinases/analysis , Cyclic AMP-Dependent Protein Kinase RIalpha Subunit/analysis ... mh:Cyclic AMP-Dependent Protein Kinase RIalpha Subunit/analysis (1) Order by. Year (decreasing). Relevance. Year (increasing) ... Cyclic AMP/analysis , Cyclic GMP-Dependent Protein Kinases/analysis , ... We studied the variation in the profile of cyclic nucleotides (cAMP, cGMP), kinases (PKA, MAPK-ERK1 / 2), phosphatase (PP2A), ...
Cyclic AMP-Dependent Protein Kinase RIalpha Subunit Type of study: Case report Limits: Adolescent / Female / Humans / Male ... Cyclic AMP-Dependent Protein Kinase RIalpha Subunit Type of study: Case report Limits: Adolescent / Female / Humans / Male ... Cyclic AMP-Dependent Protein Kinase RIalpha Subunit/genetics , Loss of Heterozygosity , Multiple Endocrine Neoplasia/genetics ...
Cyclic AMP-Dependent Protein Kinase RIalpha Subunit. Dura Mater. Female. Gene Regulatory Networks. Genotype. Humans. Male. ...
... subunit and its unique C-terminal αD helix account for this ligand swap between trypanosome PKA and canonical cAMP-dependent ... Protein kinase A (PKA) is typically activated by cAMP. Here, Bachmaier et al. show that PKA of Trypanosoma is activated by ... is a paradigm for the mechanisms of ligand-dependent and allosteric regulation in signalling. Here we report the orthologous ... The existence of eukaryotic CNB domains not associated with binding of cyclic nucleotides suggests that orphan CNB domains in ...
These accumulations were crucial for synaptic integrity and proper cAMP signaling, and were dependent on AKAP function, myosin ... Myosin V motor proteins facilitate recycling of synaptic receptors, including AMPA and acetylcholine receptors, in central and ... Cyclic AMP, Cyclic AMP-Dependent Protein Kinase RIalpha Subunit, Denervation, Mice, Mice, Inbred C57BL, Mice, Transgenic, ... A Kinase Anchor Proteins, Actins, Animals, Calcitonin Gene-Related Peptide, ...
... and a new regulatory subunit of cAMP-dependent protein kinase, RIIβ, is induced. We have previously shown that production of ... Cyclic AMP-dependent protein kinase (PKA) plays a central role in regulation of energy metabolism. Upon stimulation of ... Cyclic AMP regulates expression of the RIalpha subunit of cAMP-dependent protein kinase through an alternatively spliced 5 UTR ... Cyclic AMP-dependent protein kinase (PKA) plays a central role in regulation of energy metabolism. Upon stimulation of ...
... subunits, which contain either a substrate or a pseudosubstrate autoinhibitory domain. The human protein kinase X (PrKX) is an ... cAMP-dependent protein kinases are reversibly complexed with any of the four isoforms of regulatory (R) ... Cyclic AMP-Dependent Protein Kinase RIalpha Subunit. Sequence Homology, Amino Acid. Cyclic AMP-Dependent Protein Kinases ... Regulation of cAMP-dependent protein kinases: the human protein kinase X (PrKX) reveals the role of the catalytic subunit ...
... sequence formed by the fusion of ret tyrosine kinase and the regulatory subunit RI alpha of cyclic AMP-dependent protein kinase ... Profound ligand-independent kinase activation of fibroblast growth factor receptor 3 by the activation loop mutation ... Ligand-independent activation of tyrosine kinase in fibroblast growth factor receptor 1 by fusion with beta-galactosidase. ... Dimerization mediated through a leucine zipper activates the oncogenic potential of the met receptor tyrosine kinase. ...
1990) The expression of cAMP-dependent protein kinase subunits in primary rat hepatocyte cultures: Cyclic AMP down-regulates ... 1997) Compensatory regulation of RIalpha protein levels in protein kinase A mutant mice. J Biol Chem 272:3993-3998. ... 1981) Turnover of regulatory subunit of cyclic AMP-dependent protein kinase in S49 mouse lymphoma cells: Regulation by ... Crystal structures of catalytic subunit of cAMP-dependent protein kinase in complex with isoquinolinesulfonyl protein kinase ...
  • cAMP binds to two tandem cAMP-binding domains (CBD-A and -B) within the regulatory subunit of PKA (R), unleashing the activity of the catalytic subunit (C). While CBD-A in RIα is required for PKA inhibition and activation, CBD-B functions as a "gatekeeper" domain that modulates the control exerted by CBD-A. Preliminary evidence suggests that CBD-B dynamics are critical for its gatekeeper function. (nih.gov)
  • Identification and Characterization of Novel Mutations in the Human Gene Encoding the Catalytic Subunit Calpha of Protein Kinase A (PKA). (uio.no)
  • Involvement of the catalytic subunit of protein kinase A and of HA95 in pre-mRNA splicing. (uio.no)
  • Undifferentiated NT2 cells expressed mainly cytoplasmic PKA type I, consisting of the regulatory subunit RIalpha and the catalytic subunit Calpha. (uio.no)
  • Identification of novel splice variants of the human catalytic subunit cbeta of cAMP-dependent protein kinase. (uio.no)
  • Four different isoforms of the catalytic subunit of cAMP-dependent protein kinase, termed Calpha, Cbeta,Cgamma and PrKX have been identified. (uio.no)
  • Evolution of the cAMP-dependent protein kinase (PKA) catalytic subunit isoforms.Søberg K, Moen LV, Skålhegg BS, Laerdahl JK. (uio.no)
  • Regulation of cAMP-dependent protein kinases: the human protein kinase X (PrKX) reveals the role of the catalytic subunit alphaH-alphaI loop. (ox.ac.uk)
  • PKI is a small, heat-stable protein with high affinity for the catalytic subunit of PKA, and binding of PKI to the catalytic subunit inhibits its activity ( 15 , 23 ). (asm.org)
  • PKI is capable of freely entering the nucleus and actively shuttling the catalytic subunit of PKA back to the cytoplasm, where PKA regulatory subunits are located. (asm.org)
  • One difference between PKA-I and PKA-II is in their inhibitory domain, which blocks the catalytic subunit. (biologists.org)
  • cAMP-dependent protein kinase type I-alpha regulatory subunit is an enzyme that in humans is encoded by the PRKAR1A gene. (wikipedia.org)
  • Carney complex (CNC) is an autosomal dominant multiple neoplasia, caused mostly by inactivating mutations of the regulatory subunit 1A of the protein kinase A (PRKAR1A). (cdc.gov)
  • The "complex of myxomas, spotty skin pigmentation, and endocrine overactivity," or "Carney complex" (CNC), is caused by inactivating mutations of the regulatory subunit type 1A of the cAMP-dependent protein kinase (PRKAR1A) gene and as yet unknown defect(s) in other gene(s). (cdc.gov)
  • Most PRKAR1A mutations (82%) led to lack of detectable mutant protein (nonexpressed mutations) because of nonsense mRNA mediated decay. (cdc.gov)
  • The human PRKAR1A gene encodes the regulatory subunit 1-alpha (RIalpha) of the cAMP-dependent protein kinase A (PKA) holoenzyme. (semanticscholar.org)
  • Protein kinase A effects of an expressed PRKAR1A mutation associated with aggressive tumors. (semanticscholar.org)
  • PRKAR1A ) lead to altered kinase activity, primary pigmented nodular adrenocortical disease, and tumors of the thyroid and other tissues. (aacrjournals.org)
  • 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. (aacrjournals.org)
  • These were associated with allelic losses of the mouse chromosome 11 Prkar1a locus, an increase in total type II PKA activity, and higher RIIβ protein levels. (aacrjournals.org)
  • This mouse provides a novel, useful tool for the investigation of cyclic AMP, RIα, and PKA functions and confirms the critical role of Prkar1a in tumorigenesis in endocrine and other tissues. (aacrjournals.org)
  • PRKAR1A mutation causing pituitary-dependent Cushing disease in a patient with Carney complex. (semanticscholar.org)
  • Cell growth is regulated by various peptide growth factors through receptor-linked multiple intracellular signal-transduction pathways, such as the cyclic adenosine monophosphate (cAMP) pathway. (nih.gov)
  • Protein Kinase A (PKA) is the major receptor for the cyclic adenosine monophosphate (cAMP) secondary messenger in eukaryotes. (nih.gov)
  • Here, we demonstrate that another ubiquitous second messenger, namely, 3'-5' cyclic adenosine monophosphate (cAMP), plays a central role in regulating cytosolic Ca 2+ levels and microneme secretion during merozoite invasion of red blood cells. (prolekare.cz)
  • Lando M, Abemayor E, Verity MA, Sidell N (1990) "Modulation of intracellular cyclic adenosine monophosphate levels and the differentiation response of human neuroblastoma cells" Cancer Res. (proteinkinase.biz)
  • Adenosine can be linked to a chain of one, two, or three phosphate groups to form adenosine monophosphate (AMP), adenosine diphosphate (ADP), or adenosine triphosphate (ATP). (thefreedictionary.com)
  • adenosine monophosphate (AMP) a nucleotide, adenosine 5′-phosphate, involved in energy metabolism and nucleotide synthesis. (thefreedictionary.com)
  • The inactive holoenzyme of PKA is a tetramer composed of two regulatory and two catalytic subunits. (wikipedia.org)
  • cAMP causes the dissociation of the inactive holoenzyme into a dimer of regulatory subunits bound to four cAMP and two free monomeric catalytic subunits. (wikipedia.org)
  • In the absence of cAMP, PKA exists as an inactive tetrameric holoenzyme with the homodimeric R-subunits bound to two catalytic (C) subunits. (pubmedcentralcanada.ca)
  • The inactive PKA holoenzyme is a complex of regulatory (PKAR) and catalytic (PKAC) subunits, either as R-C heterodimer or R 2 -2C heterotetramer. (nature.com)
  • The inactive holoenzyme of PKA consists of two regulatory (R) and two catalytic (C) subunits. (aspetjournals.org)
  • On activation by cAMP binding to the R subunits, the holoenzyme dissociates into an R dimer and two free, active C subunits that can then phosphorylate target proteins. (aspetjournals.org)
  • Different isoforms of the full-length protein kinase A (PKA) regulatory subunit homodimer (R2) and the catalytic (C) subunit-bound holoenzyme (R2C2) have very different global structures despite similar molecular weights and domain organization within their primary sequences. (utah.edu)
  • These data implicate the C helix of RIalpha in modulating isoform-specific interdomain communication in the PKA holoenzyme, adding another layer of structural complexity to our understanding of signaling dynamics in this multisubunit, multidomain protein kinase. (utah.edu)
  • In the absence of cAMP, inactive Protein kinase A is a holoenzyme (PKA), a heterotetramer of two identical catalytic subunits (Pka-C) and two identical regulatory subunits (Pka-R). When cAMP is present, it binds to the regulatory subunits and releases catalytic subunits from the holoenzyme, allowing phosphorylation of target substrates. (sdbonline.org)
  • This sequestration is achieved through A-kinase anchoring proteins (AKAPs), a heterogeneous family of proteins that bind to PKA regulatory subunits and anchor PKA holoenzyme (Scott, 1994). (sdbonline.org)
  • We studied the variation in the profile of cyclic nucleotides (cAMP, cGMP), kinases (PKA, MAPK-ERK1 / 2), phosphatase (PP2A), as well as the profile of phosphorylated, S-nitrosylated and nitrated proteins up to 6 h. onset of amastigogenesis. (bvsalud.org)
  • 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. (nature.com)
  • In eukaryotes, CNB domains are bound and regulated by cyclic nucleotides. (nature.com)
  • The cAMP-dependent protein kinase (PKA) is targeted to specific subcellular compartments through its interaction with A-kinase anchoring proteins (AKAPs). (embl-heidelberg.de)
  • AKAPs contain an amphipathic helix domain that binds to the type II regulatory subunit of PKA (RII). (embl-heidelberg.de)
  • These data suggest that sperm contains several proteins that bind to AKAPs in a manner similar to RII and imply that AKAPs may have additional and perhaps unique functions in spermatozoa. (embl-heidelberg.de)
  • cAMP-dependent protein kinase is targeted to discrete subcellular locations by a family of specific anchor proteins (A-kinase anchor proteins, AKAPs). (embl-heidelberg.de)
  • Although AKAPs have been identified on the basis of their interaction with PKA, they also bind other signaling molecules, mainly phosphatases and kinases, that regulate AKAP targeting and activate other signal transduction pathways.We suggest that AKAP forms a "transduceosome" by acting as an autonomous multivalent scaffold that assembles and integrates signals derived from multiple pathways. (embl-heidelberg.de)
  • 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). (nature.com)
  • This specificity is largely achieved by binding of PKA to protein scaffolds, whereby a distinct group of proteins called A kinase anchoring proteins (AKAPs) play a dominant role. (mcponline.org)
  • AKAPs are a diverse family of proteins that all bind via a small PKA binding domain to the regulatory subunits of PKA. (mcponline.org)
  • The binding affinities between PKA and several AKAPs can be different for different isoforms of the regulatory subunits of PKA. (mcponline.org)
  • We were able to enrich all four isoforms of the regulatory subunits of PKA and concomitantly identify more than 10 AKAPs. (mcponline.org)
  • Some of the best described scaffolding proteins are the so-called A-kinase anchoring proteins (AKAPs), which all bind specifically to the N-terminal dimerization domain of the PKA regulatory domain. (mcponline.org)
  • RI and RII subunits are known to bind to AKAPs with distinct levels of affinity adding another level of intracellular organization for PKA and also facilitating the diversity of the cAMP-mediated signal transduction pathways. (mcponline.org)
  • Although cAMP elevation may occur over a large area of a target-organ cell, its effects are often more restricted due to local concentration of its main effector, protein kinase A (PKA), through A-kinase anchoring proteins (AKAPs). (deepdyve.com)
  • Blass, Kronfeld, Kazimirsky, Blumberg, Brodie: Tyrosine phosphorylation of protein kinase Cdelta is essential for its apoptotic effect in response to etoposide. (antibodies-online.com)
  • RI alpha-ret transcripts encode two isoforms of the chimeric protein (p76 and p81), which display constitutive tyrosine phosphorylation as well as a tyrosine kinase enzymatic activity. (asm.org)
  • cAMP exerts its effects by activating the cAMP-dependent protein kinase A (PKA), which transduces the signal through phosphorylation of different target proteins. (wikipedia.org)
  • PKA could be implicated in the establishment and/or maintenance of the unique pattern of gene expression occurring at the junction, or in the modulation of synaptic activity via protein phosphorylation. (rupress.org)
  • Here, we report that the PKA-RII-specific AKAP inhibitory peptide AKAP-IS perturbs the distribution of PKA-RII and diminishes the PKA-dependent phosphorylation of HERG protein. (deepdyve.com)
  • Protein phosphorylation, which plays a key role in most cellular activities, is a reversible process mediated by protein kinases and phosphoprotein phosphatases. (embl-heidelberg.de)
  • Phosphorylation usually results in a functional change of the target protein by changing enzyme activity, cellular location, or association with other proteins. (embl-heidelberg.de)
  • AGC kinase proteins are characterised by three conserved phosphorylation sites that critically regulate their function. (embl-heidelberg.de)
  • The two other phosphorylation sites are located outside the kinase domain in a conserved region on its C-terminal side, the AGC-kinase C-terminal domain. (embl-heidelberg.de)
  • Isoform-specific PKA reporters showed in sensory-neuron-derived F11 cells that the inflammatory mediator PGE 2 specifically activated PKA-II but not PKA-I. Accordingly, pain-sensitizing inflammatory mediators and activators of PKA increased the phosphorylation of RII subunits (pRII) in subgroups of primary sensory neurons. (biologists.org)
  • Increase of pRII was followed by phosphorylation of CREB in a PKA-dependent manner. (biologists.org)
  • Thus, we propose RII phosphorylation to represent an isoform-specific readout for endogenous PKA-II activity in vivo , suggest RIIβ as a novel nociceptive subgroup marker, and extend the current model of PKA-II activation by introducing a PP2A-dependent basal state. (biologists.org)
  • Ideal inhibitors such as Rp-cAMPS are those that preferentially "select" inactive conformations of target proteins by satisfying all "binding" constraints alone without inducing conformational changes necessary for activation. (pubmedcentralcanada.ca)
  • Stable isotope labeling was used to confidently identify and differentially quantify target proteins and their preferential binding affinity for the three different cAMP analogs. (mcponline.org)
  • Cyclic AMP-dependent protein kinase (PKA) plays a central role in regulation of energy metabolism. (biomedcentral.com)
  • 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. (nature.com)
  • 7500 members that confers ligand-dependent allosteric regulation to a diverse range of proteins 2 . (nature.com)
  • The PKA subunit down-regulation was blocked, however, by treatment of the cells with Leu-Leu-Leu or lactacystin, inhibitors of proteasomes that are implicated in the regulated proteolysis of specific cellular proteins. (aspetjournals.org)
  • Together, these findings demonstrate that regulation of PKA subunit expression by forskolin or a cAMP antagonist occurs primarily through post-transcriptional mechanisms and suggests the involvement of proteasome-mediated degradation in these phenomena. (aspetjournals.org)
  • A large number of G protein-coupled receptors are known to elicit diverse physiological effects in the brain via regulation of the cAMP pathway. (aspetjournals.org)
  • Regulation of immunoglobulin-$\mu$ (Ig-$\mu$) was protein kinase-mediated, whereas major histocompatibility complex (MHC) class I and class II genes, heat shock protein 70 and the PKA regulatory subunits were all protein kinase-mediated as well as labile protein-dependent. (illinois.edu)
  • Regulation of the catalytic activity of PKA is the only well-studied function of RIalpha. (semanticscholar.org)
  • The PKR regulatory subunit of protein kinase A (PKA) is involved in the regulation of growth, sexual and asexual development, and pathogenesis in Fusarium graminearum. (semanticscholar.org)
  • AKAP200 is a Drosophila melanogaster member of the "A Kinase Associated Protein" family of scaffolding proteins, known for their role in the spatial and temporal regulation of Protein Kinase A (PKA) in multiple signaling contexts. (sdbonline.org)
  • The transcript levels increase upon denervation of the muscle, but the RNA remains localized, indicating a regulation pattern similar to that of the epsilon subunit of nicotinic acetylcholine receptor. (rupress.org)
  • The functional consequence of AKAP-IS is a reversal of cAMP-dependent regulation of HERG channel activity. (deepdyve.com)
  • Thus, the in vivo activation of ret in human papillary thyroid carcinomas is provided by the fusion of its tyrosine kinase domain with different genes and can be mediated by different mechanisms of gene rearrangement. (asm.org)
  • This protein was found to be a tissue-specific extinguisher that down-regulates the expression of seven liver genes in hepatoma x fibroblast hybrids Three alternatively spliced transcript variants encoding the same protein have been observed. (wikipedia.org)
  • We have demonstrated that expression of CAAT/Enhancer binding protein β (C/EBPβ) is induced by cAMP with rapid kinetics in Sertoli cells, and that C/EBPβ is responsible for induction of late response genes like the RIIβ-gene [ 17 ]. (biomedcentral.com)
  • Our previous GeneChip data showed that EdTx downregulated MPhi genes involved in actin cytoskeleton remodeling, including protein kinase A (PKA). (genes2cognition.org)
  • The protein kinase inhibitor (PKI) family includes three genes encoding small, heat-stable inhibitors of the cyclic AMP-dependent kinase PKA. (asm.org)
  • CNBs function as regulatory modules in different classes of proteins, such as catabolite activator protein, cyclic nucleotide gated channels, Epac proteins, and guanine-nucleotide-exchange factors, where effector protein and domain activity is controlled by cAMP binding to CNB ( 3 ). (pubmedcentralcanada.ca)
  • 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. (prolekare.cz)
  • We propose that in vivo, activation of endogenous protein kinase pathways are sufficient to induce a break from retroviral latency by activating BLV transcription and the early stage of the life cycle. (illinois.edu)
  • Protein kinase A regulates the Ras, Rap1 and TORC2 pathways in response to the chemoattractant cAMP in Dictyostelium. (semanticscholar.org)
  • Bacillus anthracis edema toxin suppresses human macrophage phagocytosis and cytoskeletal remodeling via the protein kinase A and exchange protein activated by cyclic AMP pathways. (genes2cognition.org)
  • The molecular pathways involved in the aetiology of these syndromes have recently been more clearly defined and several major cellular signalling pathways are probably involved: the protein kinase A (PKA) pathway in Carney complex (CNC), the Ras/Erk MAP kinase pathway in LEOPARD/Noonan syndromes, and the mammalian target of rapamycin pathway (mTOR) in Peutz-Jeghers syndrome and the diseases caused by PTEN mutations. (bmj.com)
  • The cyclic nucleotide binding (CNB) domain regulates signaling pathways in both eukaryotes and prokaryotes. (biomedcentral.com)
  • PKA is the only known example where cAMP-dependent conformational changes lead to dissociation of the effector protein (C-subunit), whereas in all other CNB-containing proteins, the consequences of cAMP removal and binding result in induced conformational changes without dissociation of the target domains and proteins ( 3 ). (pubmedcentralcanada.ca)
  • 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 ). (mcponline.org)
  • The CNB domain is ubiquitous in eukaryotes and controls a variety of cellular functions in a cAMP/cGMP dependent manner. (biomedcentral.com)
  • The AGC (cAMP-dependent, cGMP-dependent and protein kinase C) protein kinase family embraces a collection of protein kinases that display a high degree of sequence similarity within their respective kinase domains. (embl-heidelberg.de)
  • cAMP- and cGMP-dependent protein kinases (cAPK and cGPK) contain two tandem copies of the cyclic nucleotide-binding domain. (embl.de)
  • It produces edema toxin (EdTx), a powerful adenylate cyclase that increases cyclic AMP (cAMP) levels in host cells. (genes2cognition.org)
  • The human 5-ht5A receptor couples to Gi/Go proteins and inhibits adenylate cyclase in HEK 293 cells. (wikipathways.org)
  • This activates an enzyme, adenylate cyclase, which produces cyclic AMP from ATP. (thefreedictionary.com)
  • A rise in cAMP activates protein kinase A (PKA), which regulates microneme secretion. (prolekare.cz)
  • 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. (prolekare.cz)
  • Previous physiological and pharmacological experiments have demonstrated that the Chlamydomonas flagellar axoneme contains a cAMP-dependent protein kinase (PKA) that regulates axonemal motility and dynein activity. (embl-heidelberg.de)
  • 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] . (prolekare.cz)
  • These proteins, ropporin (a protein previously shown to interact with the Rho signaling pathway) and AKAP-associated sperm protein, are 39% identical to each other and share a strong sequence similarity with the conserved domain on the N terminus of RII that is involved in dimerization and AKAP binding. (embl-heidelberg.de)
  • The participation of NO in signal transduction during amastigogenesis, suggested by unpublished data from our group, as well as the cAMP-dependent signaling pathway, were the focus of the present study. (bvsalud.org)
  • Many other proteins and enzymes modulate this pathway, including PKI, a highly specific inhibitor of PKA. (asm.org)
  • However, inhibition of the PKA catalytic activity does not mimic these peptides, suggesting that the peptides are disrupting the interaction of AKAP(s) with proteins other than PKA. (embl-heidelberg.de)
  • Flagellar radial spoke protein 3 is an A-kinase anchoring protein (AKAP). (embl-heidelberg.de)
  • Here we test the hypothesis that the axoneme contains an A-kinase anchoring protein (AKAP). (embl-heidelberg.de)
  • These accumulations were crucial for synaptic integrity and proper cAMP signaling, and were dependent on AKAP function, myosin Va, and an intact actin cytoskeleton. (ox.ac.uk)
  • In this study, we found that CD99 and soluble adenylyl cyclase (sAC) interact at endothelial borders with PKA through the A-kinase anchoring protein (AKAP) ezrin. (rupress.org)
  • In further support of AKAP-mediated targeting of kinase to HERG, PKA activity was coprecipitated from HERG expressed in HEK cells. (deepdyve.com)
  • Accumulation in fetal muscle and localization to the neuromuscular junction of cAMP-dependent protein kinase A regulatory and catalytic subunits RI alpha and C alpha. (rupress.org)
  • These isoenzymes differ in their biochemical properties, expression pattern, interacting proteins, as well as their subcellular localization ( Pidoux and Taskén, 2010 ). (biologists.org)
  • cAMP-dependent protein kinases are reversibly complexed with any of the four isoforms of regulatory (R) subunits, which contain either a substrate or a pseudosubstrate autoinhibitory domain. (ox.ac.uk)
  • 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. (nature.com)
  • Protein kinases catalyse the transfer of the gamma phosphate from nucleotide triphosphates (often ATP) to one or more amino acid residues in a protein substrate side chain, resulting in a conformational change affecting protein function. (embl-heidelberg.de)
  • Van Kolen, Slegers: Atypical PKCzeta is involved in RhoA-dependent mitogenic signaling by the P2Y(12) receptor in C6 cells. (antibodies-online.com)
  • PKA is the main intracellular cyclic AMP receptor, and its RI alpha subunit gene is located on chromosome 17q. (asm.org)
  • Dimerization mediated through a leucine zipper activates the oncogenic potential of the met receptor tyrosine kinase. (wikidata.org)
  • TEL‐induced oligomerization is shown to be essential for the constitutive activation of the protein kinase activity and mitogenic properties of TEL-platelet derived growth factor receptor β (PDGFRβ), a fusion oncoprotein characteristic of the leukemic cells of chronic myelomonocytic leukemia harboring a t(5;12) chromosomal translocation. (embopress.org)
  • Specific G protein activation and mu-opioid receptor internalization caused by morphine, DAMGO and endomorphin I. (wikipathways.org)
  • The best studied of these proteins is the prokaryotic catabolite gene activator (also known as the cAMP receptor protein) (gene crp) where such a domain is known to be composed of three alpha-helices and a distinctive eight-stranded, antiparallel beta-barrel structure. (embl.de)
  • This decrease in PKA subunit immunoreactivity was not attenuated by pretreatment of the cells with the protein synthesis inhibitor cycloheximide. (aspetjournals.org)
  • Serum-induced BLV expression was inhibited in PBL in a dose dependent fashion by the protein kinase A (PKA) inhibitor H-89. (illinois.edu)
  • Although the PKA-R isoforms differ in functionality, they share a similar overall organization i.e. a dimerization domain, the catalytic subunits inhibitor region, and two cAMP binding domains. (mcponline.org)
  • The deltaR-C heterodimer complexes studied here were each formed with a monomeric N-terminal deletion mutant of the R subunit (deltaR) that contains the inhibitor sequence and both cAMP-binding domains. (utah.edu)
  • The scattering data show that type IIalpha and type IIbeta deltaR-C heterodimers are relatively compact and globular, with the C subunit contacting the inhibitor sequence and both cAMP-binding domains. (utah.edu)
  • In contrast, the type Ialpha heterodimer is significantly more extended, with the C subunit interacting with the inhibitor sequence and cAMP-binding domain A, whereas domain B extends out such that its surface is almost completely solvent exposed. (utah.edu)
  • Exposure of CATH.a and SH-SY5Y cells to forskolin, a direct activator of adenylyl cyclase, resulted in a time-dependent decrease in levels of immunoreactivity of C and the two types of R (RI and RII). (aspetjournals.org)
  • Activator of protein kinase A (cyclic AMP agonist). (biolog.de)
  • Catabolite gene activator protein (CAP) is a prokaryotic homologue of eukaryotic cNMP-binding domains, present in ion channels, and cNMP-dependent kinases. (embl.de)
  • The 3 angstrom resolution crystal structure of the Escherichia coli catabolite gene activator protein (CAP) complexed with a 30-base pair DNA sequence shows that the DNA is bent by 90 degrees. (embl.de)
  • Protein kinase A, a ubiquitous, highly conserved serine-threonine kinase, is a key intracellular transducer of many hormonal and other extracellular signals. (sdbonline.org)
  • Molecular characterization of a thyroid tumor-specific transforming sequence formed by the fusion of ret tyrosine kinase and the regulatory subunit RI alpha of cyclic AMP-dependent protein kinase A. (asm.org)
  • 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] . (prolekare.cz)
  • A co-crystal structure of trypanosome PKA with 7-cyano-7-deazainosine and molecular docking show how substitution of key amino acids in both CNB domains of the regulatory subunit and its unique C-terminal αD helix account for this ligand swap between trypanosome PKA and canonical cAMP-dependent PKAs. (nature.com)
  • Knowledge about the molecular structure of protein kinase A (PKA) isoforms is substantial. (biologists.org)
  • Germline, protein-truncating mutations of phosphodiesterase type 11A (PDE11A) have been described to predispose to a variety of endocrine tumors, including adrenal and testicular tumors. (cdc.gov)
  • Many of the key parasite proteins that bind host receptors are localized in apical organelles called micronemes. (prolekare.cz)
  • Several other proteins such as cyclic nucleotide gated ion channels ( 1 ), phosphodiesterases (PDE) ( 2 ), and guanine nucleotide exchange factors (Epac) ( 3 ) bind cAMP. (mcponline.org)
  • Conformationally dynamic C helix of the RIalpha subunit of protein kinase A mediates isoform-specific domain reorganization upon C subunit binding. (utah.edu)
  • Pka-RI a or Pka-RIß) but Drosophila has only one isoform of each type of regulatory subunit. (sdbonline.org)
  • Considerably higher resistance against cyclic nucleotide phosphodiesterases compared to dibutyryl- or 8-Br-cAMP (Cat. (biolog.de)
  • Whereas RI subunits block the C-subunits by a non-phosphorylatable pseudosubstrate, RII subunits carry a serine within that inhibitory domain rendering them substrates of C-subunits. (biologists.org)
  • cAMP activates cAMP-dependent protein kinase A (PKA) either to stimulate or inhibit cell growth. (nih.gov)
  • Data show that laminin alpha2beta1gamma1 (Lm211) can inhibit neuregulin 1 (show NRG1 ELISA Kits ) type III (Nrg1III) by limiting protein kinase A (PKA) activation, which is required to initiate myelination. (antibodies-online.com)
  • Induction of Cbeta splice variants and formation of novel forms of protein kinase A type II holoenzymes during retinoic acid-induced differentiation of human NT2 cells. (uio.no)
  • Identification of sperm-specific proteins that interact with A-kinase anchoring proteins in a manner similar to the type II regulatory subunit of PKA. (embl-heidelberg.de)
  • Depletion of type IA regulatory subunit (RIalpha) of protein kinase A (PKA) in mammalian cells and tissues activates mTOR and causes autophagic deficiency. (semanticscholar.org)
  • Loss of the Ca2+/calmodulin-dependent protein kinase type IV in dopaminoceptive neurons enhances behavioral effects of cocaine. (wikipathways.org)
  • In metazoans (except C. elegans ), the PKA regulatory subunits are of two types: type I (Pka-RI) or type II (Pka-RII). (sdbonline.org)
  • Mammals have two isoforms of each type of regulatory subunit (e.g. (sdbonline.org)
  • A 14.4-kDa cAMP-binding fragment was generated during bacterial expression and purification of recombinant bovine cAMP-dependent protein kinase type I alpha regulatory subunit (RI alpha). (embl.de)
  • A plasmid encoding only the isolated B domain was overexpressed in Escherichia coli, and a monomeric form of the B domain was purified that had identical properties to the proteolytically generated fragment, indicating that all of the elements for the high-affinity cAMP-binding B domain are contained within the 128 amino acid carboxyl terminus of the R subunit. (embl.de)
  • These results indicate that the amino‐terminal domain conserved in a subset of the ETS proteins has evolved to generate a specialized protein-protein interaction interface which is likely to be an important determinant of their specificity as transcriptional regulators. (embopress.org)
  • Dual specificity protein kinases (e.g. (embl-heidelberg.de)
  • Prolonged induction of the B domain in E. coli or storage of the purified protein resulted in the formation of a dimer that could be reverted to the monomer by incubation in 2-mercaptoethanol. (embl.de)
  • We show that during TEM, endothelial cell (EC) CD99 activates protein kinase A (PKA) via a signaling complex formed with the lysine-rich juxtamembrane cytoplasmic tail of CD99, the A-kinase anchoring protein ezrin, and soluble adenylyl cyclase (sAC). (rupress.org)
  • The human protein kinase X (PrKX) is an exemption as it is inhibited only by pseudosubstrate inhibitors, i.e. (ox.ac.uk)
  • Detailed examination of the capacity of five PrKX-like kinases ranging from human to protozoa (Trypanosoma brucei) to form holoenzymes with. (ox.ac.uk)
  • Four regulatory (RIα, RIβ, RIIα, RIIβ) and four catalytic subunits (Cα, Cβ, Cγ, PrKX) give rise to multiple isoenzymes, categorized by their R-subunit class into PKA-I and PKA-II, respectively. (biologists.org)
  • Myosin Va cooperates with PKA RIalpha to mediate maintenance of the endplate in vivo. (ox.ac.uk)
  • We show here by co‐immunoprecipitation and GST chromatography analyses that TEL and TEL‐derived fusion proteins form homotypic oligomers in vitro and in vivo . (embopress.org)
  • Once activated, the catalytic subunits are capable of phosphorylating a large number of protein substrates, both in vitro and in vivo (Jackson, 2002 and references therein). (sdbonline.org)
  • The small angle solution scattering data presented here for three different isoforms of PKA heterodimer (deltaR-C) complexes reveal a role for another conformationally dynamic sequence in modulating inter-subunit and domain interactions, the C helix that connects the cAMP-binding domains A and B of the R subunit. (utah.edu)
  • Search, Find and Buy Antibodies, ELISA Kits and Proteins. (antibodies-online.com)
  • On www.antibodies-online.com are 49 Protein Kinase C, delta (PKCd) ELISA Kits from 10 different suppliers available. (antibodies-online.com)
  • Additionally we are shipping PKC delta Antibodies (296) and PKC delta Proteins (25) and many more products for this protein. (antibodies-online.com)
  • Ablation of the Cβ2 subunit of PKA in immune cells leads to increased susceptibility to systemic inflammation in mice. (uio.no)
  • Age-dependent development of liver fibrosis in Glmp (gt/gt) mice. (uio.no)
  • Lack of the lysosomal membrane protein, GLMP, in mice results in metabolic dysregulation in liver. (uio.no)
  • X-ray crystallography shows cAMP-bound R-subunit in the B form but surprisingly the antagonist Rp-cAMPS-bound R-subunit crystallized in the H conformation, which was previously assumed to be induced only by C-subunit-binding. (pubmedcentralcanada.ca)
  • The results indicate that the borderline methicillin-susceptible phenotype is a salt-dependent in vitro phenomenon of questionable clinical relevance. (lookformedical.com)
  • Expression of the RIIβ regulatory subunit of cAMP-dependent protein kinase is highly induced (50-fold) at the mRNA level in primary cultures of rat Sertoli cells as a late response to cAMP peaking at 12 hours [ 16 ]. (biomedcentral.com)
  • Moreover, exposure of the cell lines to forskolin had no effect on levels of mRNA for these PKA subunits over a wide time course. (aspetjournals.org)
  • Musene har ingen uttrykk av mRNA eller protein for NCU-G1. (uio.no)
  • The promiscuous enzymatic activity of the Pka-C subunit raises questions as to how cAMP-mediated signaling can achieve specific cellular responses. (sdbonline.org)
  • Two membrane proteins critical for this process are platelet/endothelial cell (EC) adhesion molecule-1 (PECAM) and CD99. (rupress.org)
  • DB-cAMP is a membrane-permeable derivative of cyclic AMP which activates the holo enzyme complex of the cAMP dependent protein kinase PKA , the Rap1 guanine-nucleotide-exchange factor Epac, cAMP-gated ion channels, CAP protein and some other target receptors. (proteinkinase.biz)
  • Velocity gradient centrifugation of solubilized porcine cardiac membrane proteins showed that several PKA-RI and PKA-RII binding proteins cosediment with ERG channels. (deepdyve.com)
  • cAMP binding to the CNBs of the R-subunits induces conformational changes, leading to dissociation of the C-subunit and activation of PKA ( 4 ). (pubmedcentralcanada.ca)
  • Further, EdTx altered the protein levels and activity of PKA and exchange protein activated by cAMP (Epac), a recently identified cAMP-binding molecule. (genes2cognition.org)