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)

Cholera toxin (choleragen) can stimulate adenylate cyclase [EC 4.6.1.1; ATP pyrophosphate-lyase (cyclizing)] activity in whole particulate fractions or purified plasma membranes of homogenates of isolated fat cells provided special precautions are taken to stabilize the enzyme during the required preincubation period. As observed with intact cells, the activation exhibits a protracted (about 25 min) lag phase, and it is blocked by ganglioside GM1 and choleragenoid ("binding" subunit of toxin). The 36,000 molecular weight subunit ("active" subunit), a hydrophobic polypeptide which does not block choleragen binding or action, can directly activate the enzyme in intact cells without a lag phase. Its effects are not blocked by ganglioside GM1 or choleragenoid, yet the stimulated activity exhibits reduced fluoride and enhanced isoproterenol sensitivity, properties characteristic of the choleragen-activated enzyme. Binding of the 125I-labeled 36,000 molecular weight subunit to cells is not saturable and is unaffected by gangliosides, choleragen, or choleragenoid, and the bound material behaves as an integral membrane protein; this protein may simply partition into the membrane matrix. With increasing time of incubation cell-bound choleragen may dissociate into its component subunits, but these remain in the membrane. Using a double antibody immunoprecipitin system, substantial precipitation of cyclase activity occurs with antisera against the 36,000 molecular weight subunit provided toxin activation has occurred. The normal process of activation may involve an initially inactive toxin--ganglioside complex which, as a result of lateral mobility and multivalent binding (lag phase), results in destabilization of the molecule with release of the "active" subunit into the membrane core where it can spontaneously associate with and perturb the cyclase complex.
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PMID:Mechanism of activation of adenylate cyclase by cholera toxin. 105 29

The muscarinic acetylcholine receptor (mAChR) is an integral membrane protein that transduces stimulus to effectors through the activation of guanine nucleotide-binding (G) proteins. Four or more subtypes of mAChR were detected in various tissues, and their primary structures were elucidated by cloning and sequence analysis of complementary DNA. Functional differences between them existed when they were expressed in clonal culture cells. mAChRI (m1) and mAChRIII (m3) preferentially activated phosphoinositide (PI) hydrolysis and opened Ca(2+)-activated K+ channels followed by closure of the M (K+)-currents, while such current activities were rarely evoked by mAChRII (m2)- and mAChRIV (m4)-transformed cells. Although it has been reported that mAChRII and mAChRIV inhibited adenylate cyclase, there was little or no such inhibition by mAChRI and mAChRIII. It is known that heart and neuronal mAChR modulate voltage-sensitive Ca2+ currents, but which species of mAChR subtypes are involved has been poorly understood. Recently we identified that endogenous mAChRIV and exogenous mAChRII expressed in NG108-15 neuroblastoma-glioma hybrid cells, but not mAChRI and mAChRIII, efficiently depressed high-threshold Ca2+ currents in a pertussis toxin-sensitive manner.
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PMID:[Coupling of muscarinic acetylcholine receptors, m1/m3 and m2/m4, to phosphoinositide metabolism and Ca2+ channels in DNA-transfected NG108-15 cells]. 172 Jul 57

The thyrotropin (TSH) receptor is an integral membrane protein which contains 2 subunits linked by a disulphide bridge. The A subunit (mol. wt. 50,000) is water soluble and forms the binding site for TSH, whereas the B subunit (mol. wt. 30,000) penetrates the lipid bilayer and probably forms the site for interaction with adenylate cyclase. Autoantibodies to the TSH receptor are found in the sera of patients with Graves' disease. The antibodies bind to the same region of the receptor's A subunit as TSH and usually act as TSH agonists, causing hyperthyroidism. Occasionally, TSH receptor autoantibodies are found which can act as TSH antagonists. Isoelectric focusing and binding studies indicate that these antibodies also bind to the same region of the receptor A subunit as TSH.
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PMID:Thyrotropin receptor antibodies. 300 8

The phosphotransferase system (PTS) in Escherichia coli is a multifunctional, multicomponent enzyme system. Its primary functions deal with carbon source acquisition, while its secondary functions are concerned with the regulation of bacterial physiology. The primary functions of the system include 1) extracellular detection, 2) unidirectional and exchange transmembrane transport, and 3) phosphoenolpyruvate-dependent and sugar phosphate-dependent phosphorylation of the sugar substrates of the system. The secondary functions include 1) regulation of the activities of adenylate cyclase and various non-PTS permeases and 2) regulation of the induced synthesis of several PTS enzymes. Both the primary and secondary functions appear to be elicited by the binding of a sugar substrate to an Enzyme II complex. One of these integral transmembrane enzymes, the mannitol Enzyme II (IImtl), has been solubilized with detergent, purified to homogeneity, and reconstituted in an artificial membrane system. The molecular weight of this protein, IImtl, is 60,000 daltons. It possesses an extracellular sugar binding site and distinct intracellular combining sites for sugar phosphate and phospho-HPr. An essential sulfhydryl group and an antibody combining site are localized to the cytoplasmic surface of the enzyme, while a dextran combining site is localized to the external surface. Preliminary experiments suggest that the different functions of the Enzyme IImtl can be dissected by genetic and biochemical techniques. These studies emphasize the functional complexity of the PTS and its integral membrane protein constituents.
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PMID:Catalytic activities associated with the enzymes II of the bacterial phosphotransferase system. 701 51

Unlike most other cellular proteins, the chemoattractant receptor, cAR1, of Dictyostelium is resistant to extraction by the zwitterionic detergent, CHAPS. We exploited this property to isolate a subcellular fraction highly enriched in cAR1 by flotation of CHAPS lysates of cells in sucrose density gradients. Immunogold electron microscopy studies revealed a homogeneous preparation of membrane bilayer sheets. This preparation, designated CHAPS-insoluble floating fraction (CHIEF), also contained a defined set of 20 other proteins and a single uncharged lipid. Cell surface biotinylation and preembedding immunoelectron microscopy both confirmed the plasma membrane origin of this preparation. The cell surface phosphodiesterase (PDE) and a downstream effector of cAR1, adenylate cyclase (ACA), were specifically localized in these structures, whereas the cell adhesion molecule gp80, most of the major cell surface membrane proteins, cytoskeletal components, the actin-binding integral membrane protein ponticulin, and G-protein alpha- and beta-subunits were absent. Overall, CHIFF represents about 3-5% of cell externally exposed membrane proteins. All of these results indicate that CHIFF is derived from specialized microdomains of the plasma membrane. The method of isolation is analogous to that of caveolae. However, we were unable to detect distinct caveolae-like structures on the cell surface associated with cAR1, which showed a diffuse staining profile. The discovery of CHIFF facilitates the purification of cAR1 and related signaling proteins and the biochemical characterization of receptor-mediated processes such as G-protein activation and desensitization. It also has important implications for the "fluid mosaic" model of the plasma membrane structures.
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PMID:Identification of detergent-resistant plasma membrane microdomains in dictyostelium: enrichment of signal transduction proteins. 916 71

The beta3-adrenergic receptor is an integral membrane protein consisting of seven transmembrane domains. Unlike the beta1 and beta2 receptors, this subtype lacks the consensus phosphorylation sites required for desensitization by serine kinases. Using the rodent specific beta3 agonist BRL 35135, our initial data indicated that beta3 receptor-mediated glycerol levels progressively decreased following daily oral doses of 5 mg/kg. Therefore, we initiated studies designed to delineate the possible mechanism(s) for this decreased response. Within 3 hours following a single oral dose of BRL 35135, serum glycerol levels and UCP (uncoupling protein) RNA levels were significantly increased whereas beta3 RNA levels were significantly decreased. Rats were dosed daily for 5 days with either vehicle or BRL 35135 (5 mg/kg, p.o.) and blood samples were collected for glycerol analysis. Adipose tissue was excised for lipolysis and adenyl cyclase measurements. In addition, UCP and beta3 receptor RNA levels were assessed. No effect on adipocyte BRL 37344-stimulated adenylyl cyclase activity was observed 3 hours following the initial dose of BRL 35135. Although a slight decrease (approximately 25%) in adenylyl cyclase activity could be observed 24 hours following the initial dose, it wasn't until day 4 of dosing that a significant decrease (50%) was observed. In contrast, beta3- stimulated lipolysis in adipocytes from BRL 35135-treated rats was decreased 85% within 24 hours and this decrease persisted through four days of treatment. These data indicate that the lipolytic response to beta3 receptor activation is decreased after only a single oral dose of BRL 35135, whereas receptor-mediated adenylyl cyclase activation, although initially unaffected, also desensitizes by day four of treatment.
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PMID:Desensitization of beta3-adrenergic receptor-stimulated adenylyl cyclase activity and lipolysis in rats. 947 22