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:2.7.11.1 (protein kinase)
81,284 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Exogenous cAMP is known to induce post-aggregative differentiation in Dictyostelium discoideum under conditions that normal development is blocked. We have analysed the cyclic nucleotide specificity, the effect of modulation of the cAMP signal and the dose-response relationship of the induction of two independent markers of post-aggregative differentiation, i.e., a prespore cell-specific antigen detected by a monoclonal antibody, and the activity of glycogen phosphorylase. Our results confirm that high concentrations of cAMP (10(-6)-10(-3)M) are required for the induction of these markers. The cells are shown not to adapt to the cAMP signal. The cyclic nucleotide specificity of induction agrees with the specificity of the cell surface cAMP receptor, but is very dissimilar to the specificity of the intracellular cAMP-dependent protein kinase. It is thus unlikely that cAMP leaks into the cell and activates the cAMP-dependent protein kinase directly. Instead, the induction of post-aggregative differentiation by cAMP seems to be mediated by cell surface cAMP receptors.
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PMID:Induction of post-aggregative differentiation in Dictyostelium discoideum by cAMP. Evidence of involvement of the cell surface cAMP receptor. 299 6

The distribution of the catalytic and regulatory subunits of the cAMP-dependent protein kinase between cytoplasm and nucleus was determined during the development of Dictyostelium discoideum. In vegetative amoebae approximately 2% of the subunits were in the nucleus. During development there was an approximately 5-fold increase in total soluble cAMP-dependent protein kinase and a 15- to 30-fold increase of enzyme in the nuclear fraction. There was a reverse translocation from nucleus to cytoplasm, when Tipped Aggregates were disrupted and the resultant amoebae incubated in single-cell suspension. The addition of cAMP to these single-cell suspensions brought about the reentry of the subunits into the nucleus. The findings are discussed in relation to the potential role of the cAMP-dependent protein kinase in the regulation of mRNA and protein synthesis.
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PMID:Translocation of cAMP-dependent protein kinase to the nucleus during development of Dictyostelium discoideum. 300 50

The purified regulatory (R) and catalytic (C) subunits of cAMP dependent protein kinase (cAK) from the primitive eukaryote Dictyostelium discoideum have been compared with the homologous proteins from bovine heart by SDS-PAGE followed by Western blotting using polyclonal antibodies. No cross-reaction could be demonstrated by this technique although the slime mold subunits share several functional properties with their mammalian counterparts and are able to form functional hybrid holoenzymes.
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PMID:Comparison of the regulatory and catalytic subunits of cAMP dependent protein kinase from Dictyostelium discoideum and bovine heart using polyclonal antibodies. 301 Sep 89

The accumulation of many postaggregative mRNA species in Dictyostelium discoideum is dependent upon the continuous presence of elevated levels of cAMP. We have analyzed the cyclic nucleotide specificity of this requirement and show that it is similar to that of the cell-surface receptor and distinct from the specificity displayed by the cAMP-dependent protein kinase. The same specificity is displayed for the accumulation of two classes of prespore mRNAs (class I, early; class II, late) and a prestalk mRNA and for the shutoff of a growth-phase mRNA. Under conditions in which cAMP phosphodiesterase activity is competitively inhibited, half-maximal accumulation of prestalk mRNA can be obtained at cAMP concentrations of 320-520 nM, whereas a higher concentration, 1-2 microM, is required for half-maximal accumulation of the prespore mRNAs and shutoff of the growth-phase mRNA. These effects of cAMP and its analogues on gene expression have been obtained under conditions in which cAMP-mediated activation of adenylate cyclase is completely inhibited. We conclude that cAMP acts to stimulate postaggregative gene expression by interacting at the cell-surface receptor.
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PMID:Interaction of cAMP with the cell-surface receptor induces cell-type-specific mRNA accumulation in Dictyostelium discoideum. 301 12

We have examined protein phosphatase activities that are present during the cellular differentiation of Dictyostelium. Utilizing differential centrifugation, ion exchange, gel filtration, and concanavalin A affinity chromatography we found a number of distinct protein phosphatase activities. Three peaks of soluble Kemptide phosphatase activity and a very broad and heterogeneous soluble histone phosphatase activity were resolved by anion exchange chromatography. Histone phosphatase was associated with the particulate fraction, while Kemptide phosphatase was not. The protein phosphatase activities were able to dephosphorylate sites that had been phosphorylated by the cyclic AMP-dependent protein kinase. Therefore it is possible that their function in vivo may be to oppose the action of the cAMP-dependent protein kinase. In addition several paranitrophenyl phosphate phosphatase activities are shown to be largely separable from the protein phosphatases. An apparent heat-stable inhibitor of histone phosphatase is shown to be artifactual in that instead of interacting with the enzyme it acts by complexing with histone.
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PMID:Chromatographic resolution of soluble and particulate protein phosphatases from Dictyostelium discoideum. 301 27

We have purified two cAMP-binding proteins from developing Dictyostelium discoideum cells, which we designate as CABP-1 and CABP-2. Purified CABP-1 consists of two polypeptides of Mr 41,000 and 36,000, which we refer to as CABP-1A and CABP-1B, respectively. Although CABP-1 exhibited specificity for cAMP, it was not labeled at a detectable level when mixed with 8-azidoadenosine 3':5'-monophosphate (8-N3[3H]cAMP). Unlike CABP-1, CABP-2 was labeled efficiently with 8-N3[3H]cAMP. Purified CABP-2 has a molecular weight of 41,000 and an isoelectric point of 5.8-6.0. The physical and biochemical properties of CABP-2 suggest that it is the regulatory subunit of cAMP-dependent protein kinase described by others (de Gunzburg, J., Part, D., Guiso, N., and Veron, M. (1984) Biochemistry 23, 3805-3812; Majerfeld, J. H., Leichtling, B. H., Maligeni, J. A., Spitz, E., and Rickenberg, H. V. (1984) J. Biol. Chem. 259, 654-661). Although CABP-1A and CABP-2 have the same molecular weight, they appear to be encoded by different genes. Two-dimensional gel electrophoresis revealed that the two polypeptides had different isoelectric points. Moreover, monoclonal antibodies raised against CABP-1 did not cross-react with CABP-2. Also, in vitro translation followed by immunoprecipitation showed that these two polypeptides were derived from primary translation products. Our finding of a novel cAMP-binding protein, CABP-1, suggests that cAMP-dependent protein kinase may not be the only intracellular regulator mediating the effects of cAMP in developing D. discoideum cells.
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PMID:Identification of multiple cyclic AMP-binding proteins in developing Dictyostelium discoideum cells. 301 38

Extracellular adenosine 3',5'-cyclic monophosphate (cAMP) is required for cell-type-specific gene expression in developing Dictyostelium discoideum. We have developed a microassay for the expression of these genes, using antibodies directed against their protein products. To characterize the transduction mechanism, we have used in this assay cAMP analogues that preferentially activate either the cell-surface cAMP receptor or the internal cAMP-dependent protein kinase. N6-(aminohexyl) cAMP activates the Dictyostelium cAMP-dependent protein kinase but does not bind to the cell-surface cAMP receptor and does not cause cell-type-specific gene expression. 2'-Deoxy-cAMP does not activate the cAMP-dependent protein kinase but binds to the receptor and causes cell-type-specific gene expression. Cyclic AMP-induced accumulation of prestalk mRNA in shaking cultures still occurs in the presence of caffeine, which blocks the receptor-coupled activation of adenyl cyclase. This suggests that the extracellular cAMP induction of cell-type-specific gene expression in developing Dictyostelium cells is mediated by the cell-surface cAMP receptor and that activating adenyl cyclase by this receptor is not essential. Using the N6-(aminohexyl) cAMP to competitively inhibit phosphodiesterase, we show that 30 nM cAMP is sufficient to induce prestalk or prespore gene expression.
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PMID:cAMP induction of prespore and prestalk gene expression in Dictyostelium is mediated by the cell-surface cAMP receptor. 302 99

Extracellular molecules regulate gene expression in eucaryotes. Exogenous cyclic AMP (cAMP) affects the expression of a large number of developmentally regulated genes in Dictyostelium discoideum. Here, we determine the specificity of the receptor(s) which mediates gene expression by using analogs of cAMP. The order of potency with which these analogs affect the expression of specific genes is consistent with the specificity of their binding to a cell surface receptor and is distinct from their affinity for intracellular cAMP-dependent protein kinase. Dose-response curves with cAMP and adenosine 3',5'-monophosphorothioate, a nonhydrolyzable analog, revealed that the requirement for high concentrations of exogenous cAMP for regulating gene expression is due to the rapid degradation of cAMP by phosphodiesterase. The addition of low concentrations of cAMP (100 nM) or analogs in pulses also regulates gene expression. Both the genes that are positively regulated by exogenous cAMP and the discoidin gene, which is negatively regulated, respond to cAMP analogs to the same degree. Genes expressed in prespore or prestalk cells are also similarly regulated. These data suggest that the effects are mediated through the same receptor. The specificity of this receptor is indistinguishable from that of the well-characterized cell surface cAMP receptor.
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PMID:Pharmacological characterization of cyclic AMP receptors mediating gene regulation in Dictyostelium discoideum. 302 32

Membranes of Dictyostelium discoideum cells were incubated under phosphorylation conditions and washed, and the effects on cAMP binding to chemotactic receptors in the absence and presence of guanosine 5'-O-(3-thiotriphosphate) (GTP gamma S) were investigated. Most experiments were done with adenosine 5'-O-(3-thiotriphosphate) (ATP gamma S), which is a good substrate for many kinases, but the product, protein phosphorothioate, is not easily hydrolyzed by phosphatases. Pretreatment of membranes under phosphorylating conditions with MgATP gamma S alters the site heterogeneity of the cAMP-binding forms, without a significant effect on the total number of binding sites. A similar effect was induced by GTP gamma S under nonphosphorylation conditions. The effects of MgATP gamma S were rapid (t1/2 = 1 min), irreversible, and not induced by Mg2+ or ATP gamma S alone or by magnesium adenylyl imidodiphosphate and magnesium adenylyl (beta, gamma-methylene)diphosphate. MgATP induced a smaller inhibition than MgATP gamma S, which was potentiated by the addition of exogenous cAMP-dependent protein kinase. The effect of MgATP was rapidly reversible; reversibility was reduced by the phosphatase inhibitor NaF. These results suggest that the effects of MgATP gamma S are mediated by an endogenous protein kinase. The major 35S-thiophosphorylated band detected by sodium dodecyl sulfate-polyacrylamide gel electrophoresis was a protein with Mr = 36,000. The phosphorylation of a protein with the molecular weight of the cAMP receptor (Mr = 40,000-45,000) was not observed.
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PMID:Alteration of receptor/G-protein interaction by putative endogenous protein kinase activity in Dictyostelium discoideum membranes. 302 6

During the developmental cycle of Dictyostelium discoideum cyclic AMP functions as both a chemotactic signal for aggregation and a regulatory molecule during later events of differentiation. Morphological and biochemical data suggest that cAMP may direct cells during morphogenesis and differentiation. We utilized microtechniques to determine the stage- and cell-specific levels of the cAMP-dependent protein kinase, the probable intracellular cAMP receptor. Kinase activity was low and non-cAMP-dependent in amoebae and early aggregates but increased and became cAMP-dependent in aggregates after the formation of tight cell contacts. Maximum kinase activity and cAMP dependency occurred during the slug and culmination stages. The only differential distribution of the kinase within a single stage occurred during culmination when the activity in the stalks was approximately one-fourth of that in the prespore mass. Preliminary evidence indicates that this difference is not due to an inhibitor. In all other stages tested cAMP-dependent protein kinase activity was equal in prespore and prestalk cells.
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PMID:Distribution of cAMP-dependent protein kinase during development in Dictyostelium discoideum. 303 1


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