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Query: EC:2.7.11.11 (AMPK)
 12,425 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

A series of novel adenosine 3',5'-cyclic monophosphate (cAMP) analogues, as well as their 6-deamino and 6-nitro derivatives, were synthesized where the purine ring was replaced by indazole, benzotriazole, and benzimidazole. The 3',5'-cyclic monophosphates of indazole and benzotriazole ribofuranosides, where the sugar-phosphate moiety is attached to the N-2 nitrogen atoms of the heterocycles, were also prepared. The biological efficiency of the analogues was tested by their ability to activate purified cAMP-dependent protein kinase I (PK-I) from rabbit skeletal muscle and cAMP-dependent protein kinase II (PK-II) from bovine heart. Each cyclic nucleotide is capable of activating both PK isozymes in half-maximum concentrations (Ka) ranging from 2.0 x 10(-8) to 4.8 x 10(-6) M. The cyclic phosphate of N-1-beta-D-ribofuranosylindazole (13) proved to be a very poor activator for both PK-I and PK-II, but when indazole binds by N-2 to ribose or when the hydrogen atom at C-4 is substituted by a nitro or amino group, activities of the analogues increase considerably. The activating potencies of benzotriazole derivatives are similar to that of cAMP, irrespective of the C-4 substituents. The Ka' values of cyclic nucleotides containing benzimidazole were found to be higher for PK-II than for PK-I; e.g. the activity of 4-nitro-1-beta-D-ribofuranosylbenzimidazole 3',5'-cyclic monophosphate (32) is nearly 20 times as high for PK-II than for PK-I.
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PMID:Synthesis and enzymatic activity of some new purine ring system analogues of adenosine 3',5'-cyclic monophosphate. 133 76

The cell cycle of Saccharomyces cerevisiae contains a decision point in G1 called 'start', which is composed of two specific sites. Nutrient-starved cells arrest at the first site while pheromone-treated cells arrest at the second site. Functioning of the RAS-adenylate cyclase pathway is required for progression over the nutrient-starvation site while overactivation of the pathway renders the cells unable to arrest at this site. However, progression of cycling cells over the nutrient-starvation site does not appear to be triggered by the RAS-adenylate cyclase pathway in response to a specific stimulus, such as an exogenous nutrient. The essential function of the pathway appears to be limited to provision of a basal level of cAMP. cAMP-dependent protein kinase rather than cAMP might be the universal integrator of nutrient availability in yeast. On the other hand stimulation of the pathway in glucose-derepressed yeast cells by rapidly-fermented sugars, such as glucose, is well documented and might play a role in the control of the transition from gluconeogenic growth to fermentative growth. The initial trigger of this signalling pathway is proposed to reside in a 'glucose sensing complex' which has both a function in controlling the influx of glucose into the cell and in activating in addition to the RAS-adenylate cyclase pathway all other glucose-induced regulatory pathways in yeast. Two crucial problems remaining to be solved with respect to cell cycle control are the nature of the connection between the RAS-adenylate cyclase pathway and nitrogen-source induced progression over the nutrient-starvation site of 'start' and second the nature of the downstream processes linking the RAS-adenylate cyclase pathway to Cyclin/CDC28 controlled progression over the pheromone site of 'start'.
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PMID:The RAS-adenylate cyclase pathway and cell cycle control in Saccharomyces cerevisiae. 144 31

In Saccharomyces cerevisiae, lack of nutrients triggers a pleiotropic response characterized by accumulation of storage carbohydrates, early G1 arrest, and sporulation of a/alpha diploids. This response is thought to be mediated by RAS proteins, adenylate cyclase, and cyclic AMP (cAMP)-dependent protein kinases. This study shows that expression of the S. cerevisiae gene coding for a cytoplasmic catalase T (CTT1) is controlled by this pathway: it is regulated by the availability of nutrients. Lack of a nitrogen, sulfur, or phosphorus source causes a high-level expression of the gene. Studies with strains with mutations in the RAS-cAMP pathway and supplementation of a rca1 mutant with cAMP show that CTT1 expression is under negative control by a cAMP-dependent protein kinase and that nutrient control of CTT1 gene expression is mediated by this pathway. Strains containing a CTT1-Escherichia coli lacZ fusion gene have been used to isolate mutants with mutations in the pathway. Mutants characterized in this investigation fall into five complementation groups. Both cdc25 and ras2 alleles were identified among these mutants.
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PMID:Control of Saccharomyces cerevisiae catalase T gene (CTT1) expression by nutrient supply via the RAS-cyclic AMP pathway. 254 66

A method for the cryogenic storage of the cAMP-dependent protein kinase from bovine cardiac muscle is described. The catalytic parameters, kcat, KM, and kcat/KM are used to assess the activity of the enzyme both prior and subsequent to the freeze-thaw cycle. The enzyme is stored in cryogenic vials at -196 degrees C in liquid nitrogen. Complete retention of catalytic activity is dependent upon a rapid and efficient freeze-thaw cycle and the use of morpholinepropanesulfonic acid as the buffer. In addition, this buffer appears to eliminate the KCl- or NaCl-induced damage typically observed for enzymes stored at low temperature in phosphate buffer. As a result, morpholinepropanesulfonic acid may prove to be a more appropriate cryopreservation buffer than phosphate when the presence of salt is required for enzyme solubility or stability.
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PMID:Cryopreservation of the cyclic 3',5'-adenosine monophosphate-dependent protein kinase from bovine cardiac muscle. 273 19

Mutations in the SRA1 or SRA3 gene eliminate the requirement for either RAS gene (RAS1 or RAS2) in Saccharomyces cerevisiae. We cloned SRA1 and SRA3 and determined their DNA sequences. SRA1 encodes the regulatory subunit of the cyclic AMP (cAMP)-dependent protein kinase and therefore is identical to REG1 and BCY1. This gene is not essential, but its deletion confers many traits: reduction of glycogen accumulation, temperature sensitivity, reduced growth rate on maltose and sucrose, inability to grow on galactose and nonfermentable carbon sources, and nitrogen starvation intolerance. SRA3 is homologous to protein kinases that phosphorylate serine and threonine and likely encodes the catalytic subunit of the cAMP-dependent protein kinase. The wild-type SRA3 gene either triplicated in the chromosome or on episomal, low-copy plasmids behaves like spontaneous dominant SRA3 mutations by suppressing ras2-530 (RAS2::LEU2 disruption), cdc25, and cdc35 mutations. These findings indicate that the yeast RAS genes are dispensable if there is constitutive cAMP-dependent protein kinase activity.
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PMID:Characterization of Saccharomyces cerevisiae genes encoding subunits of cyclic AMP-dependent protein kinase. 282

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

The effects of numerous cAMP analogs present in the [3H]cAMP binding reaction on subsequent dissociation of [3H]cAMP from the regulatory subunit of cAMP-dependent protein kinase I and II were analyzed. Certain analogs with modification at either C-8 or C-2 showed relative selectivity for one (site 1) of two intrachain cAMP binding sites of both isozymes. Modification at C-6 caused selectivity for the second site (site 2). The combination of a site-1-directed and site-2-directed analog inhibited [3H]cAMP binding much more than did either analog alone. In general, there was a correlation between the site 1 selectivity and the ability of the analog to stimulate the binding of [3H]cIMP, which selects site 2. The site-1-directed analogs stimulated the initial rate of [3H]cIMP binding. The stimulatory effect was enhanced in the presence of a polycationic protein such as histone and was inhibited by high ionic strength. The type I and II isozymes exhibited large differences in analog specificity for this effect. For type I, of the analogs tested the most efficacious for stimulating [3H]cIMP binding were those containing a nitrogen atom attached to C-8, 8-aminobutylamino-cAMP being the most effective. Type II responded best to analogs containing a sulfur atom attached to C-8, 8-SH-cAMP being the most effective of those tested. The stimulatory effect was accentuated in the presence of MgATP when using type I, but this nucleotide had no effect when using type II. It is proposed that in intact tissues cAMP binding to site 1 of either isozyme stimulates the binding to site 2.
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PMID:Effect of cyclic nucleotide analogs on intrachain site I of protein kinase isozymes. 628 70

Resting cells of the fission yeast Schizosaccharomyces pombe, suspended in buffer with glucose, responded to the addition of asparagine by increasing trehalase activity. This response was preceded by a peak in cAMP concentration. The addition of the nitrogen source to resting cells, devoid of the catalytic subunit of cAMP-dependent protein kinase, produced the transient increase in cAMP but did not promote any change in trehalase activity. In the budding yeast Pachysolen tannophilus, the activation of trehalase by nitrogen source was also accompanied by a sharp peak in cAMP. These results suggest that in the two yeasts cAMP acts as a second messenger in the transduction of the nitrogen-source-induced signal causing the activation of trehalase.
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PMID:Nitrogen-source-induced activation of neutral trehalase in Schizosaccharomyces pombe and Pachysolen tannophilus: role of cAMP as second messenger. 759 Jan 77

Schizosaccharomyces pombe cells carrying a disruption in the PKA1 gene, that encodes the catalytic subunit of cAMP-dependent protein kinase (PKA), lacked the glucose- and nitrogen-source-induced activation of trehalase at stationary-phase but rised trehalase activity in response to these compounds during the exponential phase of growth. Treatment by phosphatase of either glucose- or nitrogen-source-activated trehalase resulted in trehalase deactivation suggesting that phosphorylation of the enzyme protein occurs during activation. These data indicate that in growing cells of this yeast the mechanism responsible for the activation of trehalase can be independent of interactions with free catalytic subunits of PKA and related to a signaling pathway involving a type of protein kinase different from PKA.
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PMID:Activation of neutral trehalase by glucose and nitrogen source in Schizosaccharomyces pombe strains deficient in cAMP-dependent protein kinase activity. 760 19

Protein-tyrosine phosphorylation has long been regarded as an exclusively eukaryotic phenomenon. Although some non-eukaryotes, mainly viruses, possess genes encoding protein-tyrosine kinases or protein-tyrosine phosphatases, these were probably appropriated from the eukaryotic hosts that constitute the sites of action of these enzymes. Herein we identify a gene, iphP, from the chromosome of the cyanobacterium Nostoc commune UTEX 584 that contains the His-Cys-Xaa-Ala-Gly-Xaa-Xaa-Arg sequence characteristic of known protein-tyrosine phosphatases. The expressed gene product, IphP, displayed protein-tyrosine phosphatase activity toward phosphotyrosine residues on reduced, carboxyamidomethylated, and maleylated lysozyme with optimum activity at pH 5.0. In addition, IphP dephosphorylated the phosphoseryl groups on casein that had been phosphorylated by the cAMP-dependent protein kinase. Cell lysates of N. commune probed with antibodies to phosphotyrosine indicated the presence of a tyrosine-phosphorylated protein of M(r) approximately 85 kDa. This tyrosine-phosphorylated protein was detected in cells grown in the presence of combined nitrogen but not in nitrogen-deficient media that induces the formation of differentiated N2-fixing cells (heterocysts). Together, these data suggest a role for protein-tyrosine phosphorylation in regulating cellular functions in this cyanobacterium. IphP is the first protein-tyrosine phosphatase to be discovered that is encoded by the chromosomal DNA of any prokaryote. Given the free-living nature of N. commune and the phylogenetic antiquity of the cyanobacteria, these findings suggest for the first time the existence of a protein-tyrosine phosphatase of genuine, unambiguous prokaryotic ancestry, thus raising fundamental questions as to the origin and role of tyrosine phosphorylation.
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PMID:A protein-tyrosine/serine phosphatase encoded by the genome of the cyanobacterium Nostoc commune UTEX 584. 768 25


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