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)

Dictyostelium discoideum cells contain a single ras gene (Dd-ras) that is highly homologous to mammalian ras genes. Cell transformation with a vector carrying a ras gene with a (glycine----threonine) missense mutation at position 12 causes an altered morphogenesis. Extracellular cAMP signals regulate morphogenesis and induce chemotaxis and the activation and subsequent desensitization of adenylate and guanylate cyclase. cAMP signal transduction was investigated in Dd-ras-transformed cells. Transformants that overexpress the mutated Dd-ras-Thr12 gene show normal activation and desensitization of adenylate cyclase and normal activation of guanylate cyclase. However, cAMP induces a stronger desensitization of guanylate cyclase stimulation in the Dd-ras-Thr12 transformant than in transformants overexpressing the Dd-ras-Gly12 wild-type gene or in untransformed cells. This effect was correlated with a reduced chemotactic sensitivity of the transformant expressing the mutated Dd-ras-Thr12 gene.
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PMID:Aberrant transmembrane signal transduction in Dictyostelium cells expressing a mutated ras gene. 288 43

S. cerevisiae strains containing RAS2val19, a RAS2 gene with a missense mutation analogous to one that activates the transforming potential of mammalian ras genes, have growth and biochemical properties strikingly similar to yeast strains carrying IAC or bcy1. Yeast strains carrying the IAC mutation have elevated levels of adenylate cyclase activity. bcy1 is a mutation that suppresses the lethality in adenylate cyclase deficient yeast. Yeast strains deficient in RAS function exhibit properties similar to adenylate cyclase deficient yeast. bcy1 suppresses lethality in ras1- ras2- yeast. Compared to wild-type yeast strains, intracellular cyclic AMP levels are significantly elevated in RAS2val19 strains, significantly depressed in ras2- strains, and virtually undetectable in ras1- ras2- bcy1 strains. Membranes from ras1- ras2- bcy1 yeast lack the GTP-stimulated adenylate cyclase activity present in membranes from wild-type cells, and membranes from RAS2val19 yeast strains have elevated levels of an apparently GTP-independent adenylate cyclase activity. Mixing membranes from ras1- ras2- yeast with membranes from adenylate cyclase deficient yeast reconstitutes a GTP-dependent adenylate cyclase.
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PMID:In yeast, RAS proteins are controlling elements of adenylate cyclase. 298 30

Certain tumour cells contain activated ras genes that code for 21 000 dalton proteins (p21). These proteins associate with the inner face of the plasma membrane and bind guanine nucleotides specifically. In order to determine whether p21s have functions similar to other GTP binding proteins, we investigated the regulation, by guanine nucleotides, of adenylate cyclase (AC) activity in membrane preparations isolated from fibroblasts (C127) transformed by a temperature sensitive mutant of Kirsten sarcoma virus (Ts 371). The degree of AC stimulation by GMP P(NH)P increased when these cells were shifted from the permissive temperature (33 degrees C) to the non-permissive temperature (39 degrees C). This effect was more pronounced at low Mg++ and low GMP P(NH)P concentrations. AC stimulation remained unchanged in rat fibroblasts infected with a temperature sensitive mutant of Rous Sarcoma virus. AC activity was depressed in C127 cells infected with wild type KiMSV. Our data illustrate the feasibility of correlating alterations in the AC system with ras gene expression and using such experimental approaches to elucidate the physiological functions of the p21 proteins.
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PMID:Modulation of adenylate cyclase by guanine nucleotides and Kirsten sarcoma virus mediated transformation. 298 13

This paper reviews recent data on the adenylate cyclase system of the yeast Saccharomyces cerevisiae. Since the discovery of yeast adenylate cyclase mutants and the possibility of molecular biological analysis, adenylate cyclase and the subsequent steps in the cAMP cascade have become subject of intense investigation. CYR1, the structural gene for the adenylate cyclase catalytic subunit is necessary for cell division and in diploid cells is involved in the choice between sporulation and cell division. The cell division cycle in yeast is initiated by a step called START, which has been defined by mutations causing an arrest of the cells in an unbudded state. One class of mutation causes the cell to arrest at the same stage of the cell division cycle as the pheromone implicated in conjugation. A second class causes cells to cease growth in a different manner, but one which is similar to the arrest brought about by nutient deprivation. The adenylate cyclase gene belongs to the second class and has been identified as CDC35. Two genes of the first class have been cloned and sequenced. CDC28 codes for a kinase which has homology with the src proto-oncogene family. CDC36 is partly homologous with the oncogene ets. Two genes related to the ras oncogene family have also been implicated in the control of START. START can be dissociated in two subsequent phases, the first being controlled by the AMPc system and the second including proto-oncogenes. A model in which cAMP is a positive indicator of available nutrients such as nitrogen has been constructed.(ABSTRACT TRUNCATED AT 250 WORDS)
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PMID:[Control of the cell division cycle and sporulation in Saccharomyces cerevisiae by the cyclic AMP system]. 298 30

The Ha-ras protooncogene product p21, which may be involved in control of cellular growth, is a membrane protein that binds guanine nucleotides and hydrolyzes GTP. p21 GTPase activity is stimulated by lysophosphatidylcholine; a delay in activation was observed unless p21 was incubated with the phospholipid prior to assay. Maximal activation by the phospholipid was observed over a narrow concentration range; the presence in the assay mixture of lysophosphatidylcholine at concentrations above this optimum markedly inhibited p21 GTPase. GTP hydrolysis was also stimulated, but to a lesser degree, by phosphatidylcholine. Phosphatidylinositol and phosphatidylserine did not significantly enhance GTPase activity. The stimulatory effect of phospholipid was mimicked, in part, by nonionic detergents. p21 may be related to other GTPases, the regulatory guanine nucleotide-binding G proteins of the hormone-sensitive adenylate cyclase complex and transducin of the retinal light-activated phosphodiesterase system. The G proteins and transducin are heterotrimers; the alpha subunits possess GTPase activity and the beta gamma subunit complex along with agonist-receptor complex or light-activated rhodopsin enhance GTP hydrolysis. p21 GTPase activity was slightly stimulated by rhodopsin, but, in contrast to the GTPase activity of transducin, stimulation was not light-dependent. GTP hydrolysis was enhanced somewhat by beta gamma subunit complex in the absence, but not in the presence, of rhodopsin. Like the G proteins and transducin, activity of p21 was altered by ADP-ribosylation. Modification of p21 catalyzed by an NAD: arginine ADP-ribosyltransferase purified from turkey erythrocytes decreased both GTPase activity and guanine nucleotide binding activity.
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PMID:Effects of phospholipids and ADP-ribosylation on GTP hydrolysis by Escherichia coli-synthesized Ha-ras-encoded p21. 300 95

We have analyzed the function of the only ras homolog in S. pombe detectable by Southern blotting, ras1, which is homologous to mammalian ras genes and has been cloned. We have disrupted the ras1 gene and have replaced it with ras1Val17, which corresponds to a transforming variant of mammalian ras. Loss of ras1 activity by disruption results in the complete inability to mate. The cell body of a ras1- strain is extensively deformed, and a ras1-/ras1- diploid sporulates very poorly. Unlike RAS1 and RAS2 of S. cerevisiae, ras1 of S. pombe appears to have no effect on adenylate cyclase activity. This suggests that the target enzymes presumably modulated by ras proteins in signal transduction are not the same for all organisms.
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PMID:Role of a ras homolog in the life cycle of Schizosaccharomyces pombe. 300 33

Recent studies have shown that the 21-kilodalton protein (p21) Ha-ras gene product shares sequence homology with and may exhibit biochemical properties similar to the mammalian guanine nucleotide-binding proteins. These data suggested that one of the biochemical functions of p21 in the vertebrate cell may be to regulate adenylate cyclase [ATP pyrophosphate-lyase (cyclizing), EC 4.6.1.1]. We determined both in intact NIH-3T3 murine cells and in membranes isolated from these cells that the hormone-stimulated adenylate cyclase activity of cells expressing the EJ human bladder carcinoma oncogene (EJ-ras) is significantly reduced compared with control cells. Thus, the levels of cAMP measured in the EJ-ras-transformed cells by radioimmunoassay are reduced 78% and 93% after prostaglandin and isoproterenol stimulation, respectively, compared with the levels in control cells. Treatment of the EJ-ras-transformed cells with pertussis toxin or cholera toxin did not correct the alterations in adenylate cyclase activity. Cells expressing the normal human Ha-ras gene displayed intermediate levels of adenylate cyclase hormone sensitivity; these levels of adenylate cyclase activity were greater than those in the EJ-ras-transformed cells but lower than in control cells. Hormone-stimulated adenylate cyclase activities in cells transfected with Rous sarcoma virus DNA were similar to those in control cells. These data support the hypothesis that both the normal and mutated Ha-ras p21s are related to guanine nucleotide-binding proteins.
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PMID:Reduced hormone-stimulated adenylate cyclase activity in NIH-3T3 cells expressing the EJ human bladder ras oncogene. 301 29

Saccharomyces cerevisiae contains two members of the ras gene family. Strains with disruptions of the RAS2 gene fail to grow efficiently on nonfermentable carbon sources. This growth defect can be suppressed by extragenic mutations called sra. We have isolated 79 independent suppressor mutations, 68 of which have been assigned to one of five loci. Eleven additional dominant mutations have not been assigned to a specific locus. Some sra1 and SRA4 and all SRA3 mutations were RAS independent, allowing growth of yeast cells that lack a functional RAS gene. Mutations in sra1, SRA3, SRA4 and sra6 are linked to his6, ino1, met3 and ade6, respectively. Some sra mutants have pleiotropic phenotypes that affect glycogen accumulation, sporulation, viability, respiratory capacity and suppression of two cell-division-cycle mutations, cdc25 and cdc35. The proposed functions of many of the suppressor genes are consistent with the model in which RAS activates adenylate cyclase.
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PMID:Suppressors of the ras2 mutation of Saccharomyces cerevisiae. 301 22

Many receptors, in response to ligand activation, trigger inositol phospholipid breakdown, which leads to rapid intracellular responses. The sustained activation of this pathway is believed to be at least one of the factors involved in the stimulation of cell growth and there has been much speculation that certain oncogenes use this pathway to effect uncontrolled cellular proliferation. It has been suggested, by analogy with the receptor-mediated control of adenylate cyclase, that the receptor stimulation of inositol phospholipid metabolism is mediated through a guanine nucleotide regulatory protein (G-protein) called Gp (or Np). Although such a species has not been identified, there is now strong experimental evidence that this process is mediated by a G-protein distinct from the stimulatory and inhibitory G-proteins (Gs and Gi, respectively). The ras genes code for a plasma membrane protein, p21, whose only known biochemical property is a high-affinity GTPase activity. We show here that the expression of normal p21N-ras in NIH 3T3 fibroblasts leads to the coupling of certain growth factor receptors to stimulated inositol phosphate production. We propose that the N-ras proto-oncogene encodes a protein which couples the receptors for certain growth factors to the stimulation of phospholipase C. Thus, N-ras p21 may be the putative Gp or a functionally related protein.
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PMID:Normal p21N-ras couples bombesin and other growth factor receptors to inositol phosphate production. 301 91

A model is proposed for the receptors of the VIP family peptides including a ligand and a cellular domain. Specificities of the receptors are due to different ligand binding sites. Three subgroups of the family can be distinguished accordingly: glucagon and oxyntomodulin; GIP; VIP, secretin r and hGRF, PHI and PHM. In the same species, the expression of these different sites is cell-specific resulting in a stoichiometry of the ligand-receptor interaction which is compatible with physiological regulation of cell function. Specificities of the interaction as studied by native and synthetic analogs is supported both by restricted sequences of amino acids (such as that including the N-terminal histidine residue), and membrane-induced configuration of the ligand. Identity of the receptors is related to their interactions with subunits of the adenylate cyclase system. Arguments are put forward indicating that the alpha subunit of the guanyl regulatory protein is a reasonable candidate for directly transducing to the adenylyl cyclase the information contained in the activated ligand-binding site subunits. Evidence of functional and molecular heterogeneity of the recognizing site and of the alpha subunits leads to the supposition that some types of specific complementarity is retained at this level of interaction, further enhancing the possibility of species and cell differences. On the other hand, the identities found in other sequences of the alpha and ras oncogene products extend to the receptor of the VIP family peptides a pattern of organization which is similar to that recently described for the insulin family of receptors. The role of ligand specific receptor mediated regulation in homologous or heterologous desensitization is reviewed in brief for the peptides of the VIP family as well as the appearance of the specific receptor during the ontogenesis or the cell differentiation. The co-distribution of plasma membrane receptors from other families further adds to the cell specificity resulting for each differentiated cell in unique patterns of recognizing site. Some examples of receptor-receptor interaction are given, indicating that the integration of the different signals by cells might occur at an early step through the transmembranair domain of the receptor.
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PMID:The receptors of the VIP family peptides (VIP, secretin, GRF, PHI, PHM, GIP, glucagon and oxyntomodulin). Specificities and identity. 301 7


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