Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound   Target Concepts: Gene/Protein Disease Symptom Drug Enzyme Compound

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Query: EC:4.6.1.1 (adenylate cyclase)
19,190 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The A1 adenosine receptor is the best characterized of the widely distributed purinergic receptor family. The purified brain A1 receptor is a monomeric 35- to 36-kDa glycoprotein. A1 receptors can be clearly distinguished from A2 adenosine receptors on the basis of structure activity relationships with selective ligands. Recent structure activity data suggest that subtypes of A1 (A1a, A1b, and A3) and A2 (A2a and A2b) receptors may exist. A1 receptor-mediated responses are coupled via multiple pertussis toxin-sensitive GTP binding proteins (G proteins) to many different effectors in various tissues: adenylate cyclase, phospholipase C, Na+- Ca2+ exchange, Ca2+ channels, Cl- channels, and K+ channels. The formation of calcium-mobilizing inositol phosphates can either be enhanced or inhibited. In general, adenosine has been found to act in concert with other hormones or neurotransmitters in either an inhibitory or a stimulatory way. The myriad modulatory actions of adenosine suggest that: 1) adenosine may simultaneously produce multiple effects within the same cell; and 2) activation of A1 receptors may lead to either a decrease or an increase in the coupling of other receptors to their G proteins.
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PMID:Structure and function of A1 adenosine receptors. 191 91

The diverse effects of the catecholamines (CA) epinephine and norepinephrine are mediated by a family of specific receptors (adrenergic receptors, AR). The beta-AR is a glycoprotein present in the membrane of a number of cell types. This receptor is closely associated with at least two other proteins (Gs and adenylate cyclase enzyme, AC) to form the beta-AR complex. The beta-AR recognizes the CA and is coupled to Gs which stimulates the effector enzyme AC. This enzyme converts ATP to cAMP and is the effector of the beta-AR complex. Thus the beta-AR is a G-coupled receptor which acts by raising intracellular levels of cAMP. The beta-AR is an important site of regulatory modifications through a variety of mechanisms. The best characterized is known as homologous desensitization: when the receptor is exposed to repeated stimulus by the agonist (CA), its responsiveness wanes, probably to compensate this potentially dangerous overstimulation. The gene for mammalian beta2-AR has been recently cloned and the predicted amino-acid sequence now opens the field to identification of the protein structures involved in receptor functions. The beta2-AR protein is characterized by the presence of seven membrane spanning regions. Study of the structure, function and regulation of the beta-AR will extend our knowledge of the role of beta-AR in pathological conditions and suggest new therapeutic approaches.
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PMID:Beta-adrenergic receptors: structure, function and regulation. 197 37

We have shown previously that partially purified human chorionic gonadotrophin (hCG) preparations inhibited the specific binding of 125I-labelled hLH or hCG to Candida albicans membranes at much lower concentrations than did highly purified hLH or hCG preparations. We now describe the characterization and partial purification of a heat-labile glycoprotein from commercially available gonadotrophin preparations. The factor strongly inhibited LH binding to Candida membranes, but not to sheep or pig luteal LH receptors. This material had a molecular weight of 16,000-21,000 daltons, bound strongly to CM-Sepharose at physiological pH, and could be resolved completely from hCG and from epidermal growth factor-like factors present in commercial gonadotrophin preparations. Its activity was not attenuated by a range of inhibitors specific for the four major classes of proteolytic enzymes, nor did it inhibit hormone binding by causing degradation of 125I-labelled hLH or hCG tracers. Factors which inhibited hLH binding to Candida membranes were also present in partially purified human urinary and equine serum gonadotrophin preparations and in placental extracts, but were not detected in highly purified CG of hLH preparations. The properties of this factor were similar to those described for beta-core protein, a cleavage product of the beta subunit of hCG which is a contaminant of commercial gonadotrophin preparations. Highly purified beta-core protein inhibited 125I-labelled hLH binding to Candida membranes, but not to sheep luteal binding sites. Preparations of hCG depleted of inhibitor activity could stimulate adenylate cyclase activity in Candida membranes almost five fold. In contrast, partially purified inhibitor preparations strongly inhibited basal adenylate cyclase activity (to 18% of control levels). These observations suggest that endogenous LH-like factors, perhaps similar to beta-core proteins of hCG, may play a role in the regulation of morphogenesis in Candida species.
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PMID:Characterization of a factor(s) from partially purified human gonadotrophin preparations which inhibit(s) the binding of radiolabelled human LH and human chorionic gonadotrophin to Candida albicans. 199 72

Extracellular calcium (Ca2+) is the major physiological regulator of parathyroid function; high Ca2+ decreases PTH secretion as well as reduces cAMP accumulation. There is an increasing body of evidence suggesting the presence of a receptor-like mechanism at the surface of the parathyroid cell which mediates these and other actions of Ca2+. In the present studies we used the lectin Concanavalin-A (Con-A) to investigate the possible role of carbohydrate moieties in the regulation of cAMP metabolism by Ca2+ in bovine parathyroid cells, which is thought to involve inhibition of adenylate cyclase via activation of the guanine nucleotide regulatory protein Gi. Pretreatment of parathyroid cells with Con-A for 15-60 min significantly reversed the inhibitory effect of high Ca2+ on dopamine-stimulated cAMP accumulation, reducing the inhibition at 3 mM Ca2+ from 70 +/- 3% to 30 +/- 3%. This effect was also observed in the absence of preincubation and with concentrations of Con-A as low as 40 micrograms/ml and was reversed by alpha-methyl-D-glucoside, a specific antagonist of the lectin. The lectin also reversed the inhibitory effects of Ca2+ (2-3 mM) on cAMP accumulation stimulated by isoproterenol and forskolin to a comparable extent. Prostaglandin F2 alpha-induced inhibition of cAMP accumulation (likewise mediated by Gi) was, however, not reversed by Con-A, suggesting that the lectin did not have a generalized effect on the cell surface or on receptors inhibiting adenylate cyclase. Moreover, fluoride-induced inhibition of cAMP accumulation was not reversed by Con-A, providing additional evidence that the lectin did not act at or distal to Gi (i.e. modulate Gi, adenylate cyclase, and/or phosphodiesterase). The present study suggests that Con-A may modulate the actions of extracellular Ca2+ on parathyroid secretion, possibly modifying the interaction of Ca2+ with the cell surface by affecting carbohydrate moieties that seem to be important in the Ca2(+)-sensing process. The structural element involved in Ca2+ sensing in the parathyroid cell may be a glycoprotein or closely associated with glycoproteins with carbohydrate chains containing alpha-methyl-D-glycoside.
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PMID:Effect of the lectin concanavalin-A on calcium-regulated adenosine 3',5'-monophosphate accumulation in bovine parathyroid cells. 215 77

Erythropoietin is a glycoprotein factor which specifically regulates the proliferation and differentiation of erythroid progenitor cells. We have investigated here the biochemical mechanisms of erythroid differentiation on mouse erythroleukemia SKT6 cells which can be induced to differentiate either with erythropoietin or dimethyl sulfoxide (Me2SO). cAMP-elevating agents, such as forskolin and 3-isobutyl-1-methyl-xanthine, caused spontaneous erythroid differentiation, and these agents showed the stimulatory effects on erythropoietin- or Me2SO-induced differentiation. An adenylate cyclase inhibitor, 2',5'-dideoxyadenosine, blocked erythropoietin-induced differentiation. The intracellular cAMP level was rapidly increased by addition of erythropoietin but not by Me2SO. These observations suggest that erythroid differentiation induced by erythropoietin is mediated, at least in part, through the cAMP-dependent pathway. When the effect of erythropoietin and Me2SO on the intracellular Ca2+ level was examined using fura 2, no acute change was observed. Measurements of the levels of inositol 1,4,5-trisphosphate and diacylglycerol following stimulation with erythropoietin or Me2SO showed that phosphatidylinositol turnover did not change significantly after erythropoietin stimulation but decreased gradually after Me2SO induction. Taken together, these results indicate that a complex signaling network including the cAMP-dependent pathway is involved in the erythroid differentiation process.
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PMID:Transmembrane signaling during erythropoietin- and dimethylsulfoxide-induced erythroid cell differentiation. 217 31

We have identified a new variant surface glycoprotein expression site-associated gene (ESAG) in Trypanosoma brucei, the trypanosome leucine repeat (T-LR) gene. Like most other ESAGs, it is expressed in a life cycle stage-specific manner. The N-terminal 20% of the predicted T-LR protein resembles the metal-binding domains of nucleic acid-binding proteins. The remainder is composed of leucine-rich repeats that are characteristic of protein-binding domains found in a variety of other eucaryote proteins. This is the first report of leucine-rich repeats and potential nucleic acid-binding domains on the same protein. The T-LR gene is adjacent to ESAG 4, which has homology to the catalytic domain of adenylate cyclase. This is intriguing, since yeast adenylate cyclase has a leucine-rich repeat regulatory domain. The leucine-rich repeat and putative metal-binding domains suggest a possible regulatory role that may involve adenylate cyclase activity or nucleic acid binding.
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PMID:The trypanosome leucine repeat gene in the variant surface glycoprotein expression site encodes a putative metal-binding domain and a region resembling protein-binding domains of yeast, Drosophila, and mammalian proteins. 224 64

The transcription unit of the gene for the variant specific glycoprotein (VSG) AnTat 1.3A of Trypanosoma brucei contains several associated genes (ESAGs, for Expression Site-Associated Genes), 7 of which have already been described. We report here the characterization of a further ESAG, which we term ESAG 8, present 1 kb downstream from the putative adenylate cyclase gene ESAG 4. ESAG 8 encodes a 70 kd protein whose sequence indicates that it is probably not exposed at the cell surface. With the exception of the N-terminal domain which contains a presumptive DNA-binding zinc finger, the ESAG 8 protein consists exclusively of leucine-rich repeats of 23 amino acids, typical of protein-interacting domains such as the RAS-interacting region of the yeast adenylate cyclase. ESAG 8 transcripts are only found in bloodstream forms, and their level is particularly low, suggesting a high rate of degradation. The ESAG 8 protein may be involved in stage-specific regulatory processes, such as gene expression control or adenylate cyclase activation.
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PMID:A gene from the VSG expression site of Trypanosoma brucei encodes a protein with both leucine-rich repeats and a putative zinc finger. 225 25

A1 adenosine receptors (A1AR) acting via the inhibitory guanine nucleotide binding protein inhibit adenylate cyclase activity in brain, cardiac, and adipose tissue. We now report the purification of the A1AR from bovine cerebral cortex. This A1AR is distinct from other A1ARs in that it displays an agonist potency series of N6-R-phenylisopropyladenosine (R-PIA) greater than N6-S-phenylisopropyladenosine greater than (S-PIA) greater than 5'-N-ethylcarboxamidoadenosine (NECA) compared to the traditional potency series of R-PIA greater than NECA greater than S-PIA. The A1AR was solubilized in 1% 3-[(3-cholamidopropyl)dimethylammonio]-1-propanesulfonate (Chaps) and then purified by chromatography on an antagonist [xanthine amine congener (XAC)]-coupled Affi-Gel 10 followed by hydroxylapatite chromatography. Following purification, sodium dodecyl sulfate-polyacrylamide gel electrophoresis revealed a single protein of Mr 36,000 by silver staining, Na125I iodination with chloramine T and photoaffinity labeling with [125I]8-[4-[[[[2-(4-aminophenyl acetylamino) ethyl] carbonyl] methyl] oxy]-phenyl]-1,3- dipropylxanthine. This single protein displayed all the characteristics of the A1AR, including binding an antagonist radioligand [( 3H]XAC) with high affinity (Kd = 0.7 nM) and in a saturable manner (Bmax greater than 4500 pmol/mg). Agonist competition curves demonstrated the expected bovine brain A1AR pharmacology: R-PIA greater than S-PIA greater than NECA. The overall yield from soluble preparation was 7%. The glycoprotein nature of the purified A1AR was determined with endo- and exoglycosidases. Deglycosylation with endoglycosidase F increased the mobility of the A1AR from Mr 36,000 to Mr 32,000 in a single step. The A1AR was sensitive to neuraminidase but resistant to alpha-mannosidase, suggesting the single carbohydrate chain was of the complex type. This makes the bovine brain A1AR similar to rat brain and fat A1AR in terms of its carbohydrate chains yet the purified A1AR retains its unique agonist potency series observed in membranes.
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PMID:Purification and characterization of bovine cerebral cortex A1 adenosine receptor. 227 55

Dispersed cells from rat submandibular salivary glands were incubated in medium supplemented with different fatty acids, such as stearic (18:0), oleic (cis 18:1 omega 9) and elaidic acid (trans 18:1 omega 9). The exogenous fatty acids were incorporated into the membrane lipids. A comparison of the adenylate cyclase activity in membranes of cells incubated with different fatty acids revealed the following order (from highest to lowest specific activity): stearic, elaidic, oleic. The findings suggest that changes in adenylate cyclase activity in these dispersed membranes enriched with different fatty acids may be related to the possible changes in membrane fluidity. The synthesis of glycoproteins was studied by measuring the incorporation of [1-14C]-glucosamine into TCA-PTA-precipitable material in the presence or absence of fatty acids. No effect of the exogenous fatty acids on glycoprotein synthesis was observed.
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PMID:Fatty acid incorporation into membranes of dispersed rat submandibular salivary gland cells and their effect on adenylate cyclase activity. 228 99

Human choriogonadotropin (hCG) is a heterodimeric hormone consisting of an alpha subunit and a beta subunit. hCG and aglycosylated hCG (aghCG) have similar receptor binding affinities but differ in their ability to activate hormone-responsive adenylate cyclase. aghCG is an effective antagonist. The mechanisms of this antagonism and interactions of antagonistic aghCG with the receptor are not understood. To address this critical question, we have examined the interaction of this hormone analog with the receptor. The hormone receptor on porcine granulosa cells is a glycoprotein of 86 kDa and thas three domains of 24 kDa, 28 kDa, and 34 kDa, which are disulfide-linked. They undergo proteolysis, particularly when bound to the hormones, to produce three polypeptide components. These three receptor components can readily be identified through the use of affinity labeling with the hormones. Affinity labeling with an amino-specific homobifunctional reagent and subsequent cleavage indicate that hCG is cross-linked directly to the 24-kDa receptor component. In contrast, aghCG is cross-linked directly to the 34-kDa component. The peptide map of the cross-linked aghCG-34-kDa receptor component produced by papain treatment is different from the peptide map of the cross-linked complex of hCG-24-kDa component. This difference in receptor binding may be a factor determining the success or failure of signal transduction from the receptor to the effector system, guanine nucleotide-binding regulatory protein, and adenylate cyclase.
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PMID:Differential interactions of human choriogonadotropin and its antagonistic aglycosylated analog with their receptor. 234 45


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