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 recently introduced frog olfactory cilia preparation (Chen and Lancet, 1984; Pace et al., 1985) has been useful for studies of molecular chemosensory mechanisms. Here we describe in detail the properties of this cilia preparation. The "calcium shock" procedure leads to a complete removal of the cilia from the olfactory epithelial surface. Isolated cilia constitute segments of proximal regions with 9 X 2 + 2 microtubular arrangement and a large proportion of membrane vesicles, probably derived from the ciliary distal segments. Polypeptides unique to the olfactory cilia preparation, compared to a control preparation of palate respiratory cilia, are identified by Coomassie brilliant blue staining, silver staining, and radiolabeled lectin overlays, as well as by biosynthetic labeling with 35S-methionine in epithelial explants and protein phosphorylation in isolated cilia. The olfactory cilia preparation contains odorant-sensitive adenylate cyclase, which is absent in control membranes from deciliated epithelium. High activities of tyrosine and serine/threonine protein kinases are also present. The olfactory cilia preparation described should be instrumental in the further elucidation of the biochemistry and molecular biology of vertebrate olfaction.
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PMID:Isolated frog olfactory cilia: a preparation of dendritic membranes from chemosensory neurons. 309 81

The ras proto-oncogene, found in all eukaryotes so far examined, encode s a protein with guanine nucleotide-binding and GTPase activity. Gene disruption experiments in yeast indicate that ras is essential for cell growth. Anit-sense mutagenesis approaches suggest that this is also true for Dictyostelium. Most mutations causing an amino-acid substitution for Gly 12 result in decreased GTPase activity and produce a transforming phenotype. In yeast, a Gly 19---- Val 19, missense mutation (Gly 19 is similar to Gly 12 in mammalian and Dictyostelium ras proteins) causes a series of dominant phenotypes, including elevated adenylate cyclase activity. In mammalian cells there is no evidence that ras activates adenylate cyclase activity. D. discoideum contains a single ras gene (Dd-ras) that encodes a protein very similar to the mammalian ras protein and identical to c-ras at the potentially transforming positions. Dd-ras is expressed in vegetative cells and later in development in prestalk cells whereas ras protein is found in vegetative and developing cells. In the migrating pseudoplasmodium, ras protein is found in prestalk but not prespore cells, suggesting it is involved in the function and/or differentiation of the anteriorly localized prestalk cells. In this report we examine the effects of expression of a Dd-ras gene carrying a Gly-12----Thr 12 missense mutation.
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PMID:Phenotypic changes induced by a mutated ras gene during the development of Dictyostelium transformants. 309 90

The mechanism of insulin action is only partly understood. At one end of the signalling chain, the structure of the insulin receptor is known in detail, and at the other end, insulin controls cellular metabolism by regulating the phosphorylation of serine and threonine residues in key target enzymes. The molecular events linking the occupied receptor to changes in target enzyme phosphorylation have remained obscure. Recently, insulin was shown to promote the hydrolysis of a phosphatidylinositol glycan with release of its polar head-group. The head group was reported to activate a high-affinity cyclic AMP-phosphodiesterase and pyruvate dehydrogenase, to inhibit catecholamine-stimulated lipolysis, and also to inhibit phospholipid methyltransferase and adenylate cyclase. We report here that in intact adipocytes this head-group faithfully copies the insulin-directed effects on the phosphorylation and dephosphorylation of target proteins of the hormone.
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PMID:Phospho-dephospho-control by insulin is mimicked by a phospho-oligosaccharide in adipocytes. 331 56

Recent genetic and biochemical studies of two mutants of the cAMP pathway in yeast, cyr1 and bcy1, have demonstrated that cAMP-dependent protein phosphorylation plays a major regulatory role in the control of proliferation and differentiation. As a first step in examining this regulatory system in more detail and in identifying the protein substrates of cAMP-dependent protein kinase, we have analyzed phosphoprotein patterns in the mutants cyr1-2(ts) and bcy1 by two-dimensional polyacrylamide gel electrophoresis. Our analysis has revealed several proteins whose phosphorylation is controlled positively or negatively by the cAMP pathway in yeast. The presence of some of these phosphoproteins was directly associated with proliferation (positive regulation), while that of others was correlated with cell cycle arrest (negative regulation). The phosphoprotein patterns of cyr1-2(ts) temperature-arrested cells, and nitrogen (NH+4)-starved cells, were strikingly similar, suggesting that response to NH+4 is mediated in part by adenylate cyclase. Phosphoproteins whose presence correlated with cell cycle arrest were found to be phosphorylated on serine and threonine residues, while the major phosphoproteins present predominantly in proliferating cells were phosphorylated only on serine residues. None of the greater than 20 phosphoproteins we examined contained phosphotyrosine under either growth condition.
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PMID:Identification of phosphoproteins correlated with proliferation and cell cycle arrest in Saccharomyces cerevisiae: positive and negative regulation by cAMP-dependent protein kinase. 352 46

We have constructed the yeast strain TS1, with the RAS2 gene replaced by mutant allele encoding a partially defective gene product, and with an inactive RAS1 gene. TS1 cells accumulate as unbudded cells upon temperature shift from 30 to 37 degrees C, thus showing that the RAS1 and RAS2 gene functions are important for progression through the G1 phase of the cell cycle. After the isolation of revertants able to grow at the nonpermissive temperature, we have found that a chromosomal point mutation can bypass the G1 arrest of TS1 and cdc25 cells, and the lethality of ras1 ras2 mutants. The mutation predicts the replacement of threonine by isoleucine at position 1651 of yeast adenylate cyclase. The RAS-independent, as well as the RAS-dependent adenylate cyclase activity, is increased by the mutation. Like the wild-type enzyme, the RAS-dependent activity of the mutant adenylate cyclase is turned on by the GTP-bound form of the RAS2 protein. The amino acid sequence surrounding the threonine 1651 shows similarity with protein kinase substrates. Possible implications for the function of adenylate cyclase are discussed.
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PMID:Suppression of defective RAS1 and RAS2 functions in yeast by an adenylate cyclase activated by a single amino acid change. 354 83

The beta subunit of human choriogonadotropin (hCG) was previously shown to be phosphorylated by beef skeletal muscle cAMP-dependent protein kinase (Keutmann, H. T., Ratanabanangkoon, K., Pierce, M. W., Kitzmann, K., and Ryan, R. J. (1983) J. Biol. Chem. 258, 14522-14527). The phosphorylation site was primarily at Thr 97, located within the "determinant loop" region proposed by Ward and Moore (Ward, D. N., and Moore, W. T. (1979) Animal Models for Research in Fertility and Contraception (Alexander, N. J., ed) pp. 151-164, Harper and Row, Baltimore, MD) to be important for hormonal activity and specificity. Biological and immunological studies were carried out to determine the effect of this modification on the activity of hCG. The phosphorylated hCG beta recombined with hCG alpha to form phosphorylated hCG (*hCG). The recombined *hCG retained full immunological activity in a radioimmunoassay using anti-hCG serum and 125I-hCG. The biological activities of the *hCG on appropriate rat gonadal cells, as studied by hCG radioreceptor assay, follitropin radioreceptor assay, and adenylate cyclase assay, were 0.29 +/- 0.04, 0.29 +/- 0.07, and 0.69 +/- 0.13 times as potent as hCG, respectively. The reduced receptor binding activity of *hCG was not due to dissociation of the hormone into its subunits. The far ultraviolet CD spectrum of the *hCG showed no gross conformational change induced by phosphorylation. We conclude the following: 1) Thr 97 is not involved in subunit-subunit interaction and is not part of the hCG antigenic site recognized by this particular antiserum; 2) Thr 97 does appear to participate in the hCG-receptor interactions; 3) modification of Thr 97 does not result in an enhancement of follitropin-like activity.
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PMID:Properties of the phosphorylated beta subunit of human choriogonadotropin. 619 64

The ORL1 receptor, an orphan receptor whose human and murine complementary DNAs have recently been characterized, structurally resembles opioid receptors and is negatively coupled with adenylate cyclase. ORL1 transcripts are particularly abundant in the central nervous system. Here we report the isolation, on the basis of its ability to inhibit the cyclase in a stable recombinant CHO(ORL1+) cell line, of a neuropeptide that resembles dynorphin A9 and whose amino acid sequence is Phe-Gly-Gly-Phe-Thr-Gly-Ala-Arg-Lys-Ser-Ala-Arg-Lys-Leu-Ala-Asn-Gln. The rat-brain cDNA encodes the peptide flanked by Lys-Arg proteolytic cleavage motifs. The synthetic heptadecapeptide potently inhibits adenylate cyclase in CHO(ORL1+) cells in culture and induces hyperalgesia when administered intracerebroventricularly to mice. Taken together, these data indicate that the newly discovered heptadecapeptide is an endogenous agonist of the ORL1 receptor and that it may be endowed with pro-nociceptive properties.
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PMID:Isolation and structure of the endogenous agonist of opioid receptor-like ORL1 receptor. 756 39

Mesenchymal cells are continually stimulated by a wide spectrum of biological mediators. These mediators bind to receptors on the cell surface and initiate a cascade of signaling events. The initial signal transduction pathways known to be stimulated in mesenchymal cells included phospholipase C, phospholipase D, phospholipase A2, adenylate cyclase, receptor tyrosine kinases, and receptor serine/threonine kinases. These pathways are reviewed and specific applications for therapeutic intervention in wound healing and regenerative therapy in the periodontium are discussed.
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PMID:Signal transduction mechanisms in mesenchymal cells. 770 25

The aim of this study was to achieve a better understanding of the integration in striatal medium-sized spiny neurons (MSNs) of converging signals from glutamatergic and dopaminergic afferents. The review of the literature in the first section shows that these two types of afferents not only contact the same striatal cell type, but that individual MSNs receive both a corticostriatal and a dopaminergic terminal. The most common sites of convergence are dendritic shafts and spines of MSNs with a distance between the terminals of less than 1-2 microns. The second section focuses on synaptic transmission and second messenger activation. Glutamate, the candidate transmitter of corticostriatal terminals, via different types of glutamate receptors can evoke an increase in intracellular free calcium concentrations. The net effect of dopamine in the striatum is a stimulation of adenylate cyclase activity leading to an increase in cAMP. The subsequent sections present information on calcium- and cAMP-sensitive biochemical pathways and review the regional and subcellular distribution of the components in the striatum. The specific biochemical reaction steps were formalized as simplified equilibrium equations. Parameter values of the model were chosen from published experimental data. Major results of this analysis are: at intracellular free calcium concentrations below 1 microM the stimulation of adenylate cyclase by calcium and dopamine is at least additive in the steady state. Free calcium concentrations exceeding 1 microM inhibit adenylate cyclase, which is not overcome by dopaminergic stimulation. The kinases and phosphatases studied can be divided in those that are almost exclusively calcium-sensitive (PP2B and CaMPK), and others that are modulated by both calcium and dopamine (PKA and PP1). Maximal threonine-phosphorylation of the phosphoprotein DARPP requires optimal concentrations of calcium (about 0.3 microM) and dopamine (above 5 microM). It seems favourable if the glutamate signal precedes phasic dopamine release by approximately 100 msec. The phosphorylation of MAP2 is under essentially calcium-dependent control of at least five kinases and phosphatases, which differentially affect its heterogeneous phosphorylation sites. Therefore, MAP2 could respond specifically to the spatio-temporal characteristics of different intracellular calcium fluxes. The quantitative description of the calcium- and dopamine-dependent regulation of DARPP and MAP2 provides insights into the crosstalk between glutamatergic and dopaminergic signals in striatal MSNs. Such insights constitute an important step towards a better understanding of the links between biochemical pathways, physiological processes, and behavioural consequences connected with striatal function. The relevance to long-term potentiation, reinforcement learning, and Parkinson's disease is discussed.
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PMID:Postsynaptic integration of glutamatergic and dopaminergic signals in the striatum. 783 76

To elucidate the effect of somatostatin and its mechanism of action on airway beta-adrenergic function, we studied canine bronchial smooth muscle under isometric conditions in vitro. Somatostatin (10(-6) M) inhibited the salbutamol-induced relaxation, so that the salbutamol concentration-response curves were displaced to higher concentrations (P < 0.01). This inhibition was dose dependent, the concentration of somatostatin required to produce a half-maximal effect being 10(-8) M. The relaxant responses to forskolin were likewise inhibited by somatostatin, but those to dibutyryl 3',5'--adenosine cyclic monophosphate (DB-cAMP), verapamil and nitroprusside were not. Somatostatin inhibited the salbutamol-induced accumulation of intracellular cAMP. These effects were abolished by the somatostatin antagonist cyclo [7-aminoheptanoyl-Phe-D-Trp-Lys-Thr (Bz)] or pertussis toxin. These observations suggest that somatostatin down-regulates beta-adrenergic function of airway smooth muscle through activation of an inhibitory guanine nucleotide (GTP)-binding regulatory protein, Gi, coupled to adenylate cyclase.
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PMID:Pertussis toxin-sensitive airway beta-adrenergic dysfunction by somatostatin. 790 48


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