Gene/Protein Disease Symptom Drug Enzyme Compound
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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The plasma-membrane ATPase of Saccharomyces cerevisiae is a proton pump whose activity, essential fro proliferation, is subject to regulation by nutritional signals. The previous finding that the CDC25 gene product is required for the glucose-induced H+-ATPase activation suggested that H+-ATPase activity is regulated by cAMP. Analysis of starvation-induced inactivation and glucose-induced activation of the H+-ATPase in mutants affected in activity of the RAS proteins, adenylyl cyclase or cAMP-dependent protein kinase showed that nutritional regulation of H+-ATPase activity does not depend directly on any of these factors. We conclude that adenlyl cyclase does not mediate all nutritional responses. This also indicates that the specific CDC25 requirement for the glucose-induced activation of the H+-ATPase identifies a new function for the CDC25 gene product, a function that appears to be independent of CDC25-mediated modulation of the RAS/adenylyl cyclase/cAMP pathway.
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PMID:cAMP- and RAS-independent nutritional regulation of plasma-membrane H+-ATPase activity in Saccharomyces cerevisiae. 255 50

One of the earliest events in the development of Dictyostelium discoideum is the induction of the cyclic nucleotide phosphodiesterase gene. During vegetative growth a small amount of secreted phosphodiesterase is synthesized. The phosphodiesterase transcript which is responsible for the vegetative enzyme has a size of 1800 nucleotides. Soon after starvation begins a more abundant mRNA with a size of 2200 nucleotides is synthesized by the developing cells. The induction of the 2200-nucleotide mRNA is dependent on protein synthesis and takes place under all regimens of growth and starvation. When growth is in axenic medium and development is in phosphate buffer, the appearance of the larger transcript is very rapid, occurring within 30 min after the onset of starvation. The initial burst of phosphodiesterase mRNA synthesis is followed by a decline in mRNA abundance unless the cells are stimulated by cAMP. When cells are grown on bacteria and development takes place on filter paper, the larger transcript appears after 4 hr, reaches a peak at 10-12 hr of development, and then slowly disappears. When prestalk and prespore cells from migrating slugs are separated, a small amount of transcript can be found only in the prestalk cells. A series of mutants blocked early in development make very little phosphodiesterase transcript or are otherwise abnormal in expression of the phosphodiesterase mRNA. Together these mutants define five independent genetic loci which affect the accumulation of the phosphodiesterase mRNA. These are the pdsA, fgdA, fgdC, fgdD, and fgdE genes.
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PMID:The expression of two transcripts of the phosphodiesterase gene during the development of Dictyostelium discoideum. 282 53

We have analyzed the level of substrate (AdoMet) and products (AdoHcy) of transmethylations throughout the developmental cycle of the primitive eukaryote Dictyostelium discoideum. The ratio AdoMet/AdoHcy varied dramatically during differentiation. The intracellular level of AdoHcy decreased sharply after the beginning of starvation reaching a value of 18% of that in vegative cells within 4 h. In contrast, there was a two-fold transient increase in AdoMet at the time of aggregation. However, these changes were not related to changes in AdoHcy hydrolase since constant levels of both the protein and the activity were found until 16 h of differentiation. In particular, there was no indication of an in vivo inactivation of the enzyme by cAMP at the time of aggregation. These results are discussed with respect to the previously postulated role of AdoHcy hydrolase in the regulation of the AdoMet/AdoHcy ratio in eukaryotic cells.
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PMID:S-adenosylmethionine, S-adenosylhomocysteine and S-adenosylhomocysteine hydrolase variations during differentiation of Dictyostelium discoideum. 283 54

In the preceding paper, we have identified a protein of Mr = 118,000 which is induced by stress conditions that lead to cessation of DNA synthesis and cell division (Verma, R., Iida, H., and Pardee, A.B. (1988) J. Biol. Chem. 263, 8569-8575). In the current study, we have investigated the possible role this protein may play in cellular proliferation by studying p118 expression in mutants of the cAMP metabolic pathway. The cyr 1-2 mutant gene encodes a thermolabile adenylate cyclase whose activity is only 7% of wild type even at permissive temperatures (23 degrees C). We have found that at 23 degrees C, the G1 period was 5-fold longer in cyr 1-2 than in CYR1+ cells and that p118 was constitutively expressed in these slow cycling mutants. Addition of 8-bromo-cAMP to cyr 1-2 mutants restored growth at both the restrictive and permissive temperatures and resulted in a shut-off in the synthesis of p118. The effect of the analog on p118 expression was rapid, preceding the increase in cell number and percentage-budded cells. In contrast to wild type cells, p118 synthesis was not induced by sulfur starvation in RAS2val19 mutants possessing high levels of adenylate cyclase activity and bcy1 mutants defective in the regulatory subunit of cAMP-dependent protein kinase. A large body of evidence exists supporting a role of cAMP in positive control of cell proliferation. It is therefore possible that conditions which decrease cAMP arrest growth through a chain of events that include p118 induction.
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PMID:Modulation of expression of the stress-inducible p118 of Saccharomyces cerevisiae by cAMP. II. A study of p118 expression in mutants of the cAMP cascade. 283 58

cAMP chemoattractant receptors on the surface of Dictyostelium discoideum cells are visualized by means of immunocytochemistry. Receptor antigen is virtually absent from growing cells and begins to accumulate after about 6 hr of starvation, concomitant with the increase in surface cAMP binding activity. In aggregating cells, the antigen is uniformly distributed over the cell surface. Persistent cAMP stimulation, which leads to down-regulation of cAMP binding activity, induces a striking rearrangement of receptor antigen into patches or internal vesicles. A similar patching of receptor antigen is observed during tight aggregate formation, when surface cAMP binding activity decreases. These observations indicate that receptor down-regulation involves receptor agglomeration and suggest that receptor down-regulation takes place in vivo, when tight aggregates are being formed.
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PMID:Localization of chemoattractant receptors on Dictyostelium discoideum cells during aggregation and down-regulation. 283 50

The complete nucleotide sequence of the mei2 gene of Schizosaccharomyces pombe, which is essential for initiation of meiosis, is presented and four transcriptional start sites assigned. Transcription of mei2 and other genes involved in life cycle control of S. pombe, which is inducible by nitrogen starvation, is inhibited by addition of cAMP, suggesting that cAMP can mediate the signal of nitrogen supply in S.pombe. mei2 is the furthest downstream among target genes regulated by cAMP and genetic or physiological factors so far shown to block uncontrolled meiosis in S.pombe, which is provoked by inactivation of the part1 gene product, are either mutations at the mei2 locus or inhibitors of its expression. Cooperation of two regulatory pathways, one leading to the inactivation of pat1 activity and the other to the supply of the mei2 product, appears to commit cells to meiosis in S.pombe.
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PMID:The S.pombe mei2 gene encoding a crucial molecule for commitment to meiosis is under the regulation of cAMP. 284 Feb 84

The aggregation program of Dictyostelium discoideum is extremely sensitive to the effects of tunicamycin when the drug is added to cells during the first few hours of starvation. Inhibition of development is observed with concentrations as low as 0.5 micrograms/ml, which cause only a 25%-30% inhibition of general N-linked glycosylation. However, 0.5 micrograms/ml tunicamycin can result in the total inhibition of N-linked glycosylation of specific, developmentally regulated, proteins, as exemplified by the glycoprotein 117 antigen. If added after the first hours of starvation, tunicamycin cannot inhibit aggregation even when present at 10 micrograms/ml, which maximally inhibits N-linked glycosylation. cAMP pulses can override the inhibitory effects of tunicamycin on cell aggregation. The data support the hypothesis that there is an early developmental pathway that is dependent on the N-linked glycosylation of one, or a small set of developmentally regulated proteins and that this pathway may involve the biogenesis of the chemotactic signalling system. In addition, the data raise questions as to the role of N-linked oligosaccharides in cell cohesion.
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PMID:Inhibition of N-linked glycosylation in Dictyostelium discoideum: effects of aggregate formation. 285 Feb 53

We have analyzed the effects of the cAMP relay inhibitor, caffeine, and the receptor antagonist, adenosine, on the regulation of the cell-surface cAMP receptor in suspension-starved Dictyostelium discoideum cells by measuring ammonium sulfate-stabilized binding of [3-H]cAMP to intact cells. When cells were starved in fast (230 r.p.m.) shaken suspension in 10 mM Na+/5 mM K+ phosphate buffer, pH 6.5, plus 1 mM CaCl2 and 2.5 mM MgCl2, and assayed for specific cAMP binding, receptor accumulation peaked at approximately 6 hours, reaching a maximum of 1.5 pmol cAMP bound/10(7) cells (saturation binding). Neither caffeine nor adenosine inhibited the accumulation of cAMP receptors. Similar results were obtained in caffeine-treated, slow shaken (90 r.p.m.) suspension cultures. These results suggest that starvation alone is sufficient stimulus to induce the cAMP receptor. We have also tested the effects of different buffer ionic compositions on the accumulation of cAMP receptors. Elevation of the monovalent ion concentration to 30-40 mM was found to significantly inhibit the induction of cAMP receptors.
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PMID:The effect of caffeine, adenosine, and buffer ionic composition on the induction of cell-surface cAMP binding during starvation of Dictyostelium discoideum. 285 21

We have described in D. discoideum a highly organized cell aggregation that is mediated by cAMP. After suitable differentiation induced by starvation, the cells develop the capacity to orient in gradients of cAMP and to secrete cAMP in response to cAMP. This signaling response sets up the cell-cell relay of cAMP waves that transiently orients the cells toward the center. Both the signaling response and the chemotactic response, measured in isolated cells, adapt. The kinetics and properties of adaptation of the two responses are similar and may be due to the same mechanism. The mechanism does not involve protein synthesis, a change in the number or affinity of surface receptors, or the activation of adenylate cyclase. Adaptation of signaling is essential for the oscillatory production of cAMP at the aggregation centers and ensures that the cAMP waves move steadily toward the edge of the aggregation territories. Adaptation of the chemotactic response also ensures that cells do not reorient away from the center in the gradient presented by the trailing edge of the wave. We have demonstrated that both chemotaxis and cAMP signaling are mediated by the same surface receptor. The polypeptide containing the binding site of the receptor has been identified by photoaffinity labeling with [32P]-8-N3-cAMP as a diffuse band of 41,000-45,000 Mr. The receptor and adenylate cyclase copurify on a homogeneous class of vesicles resistant to extraction by nonionic detergents. A GTP-binding protein that is a substrate for cholera toxin-catalyzed ADP ribosylation is found in supernatants and membranes and may be similar to the Gs regulatory protein of adenylate cyclase in higher organisms. The mechanism of activation of the adenylate cyclase and chemotactic machinery is unknown. We have been able to inhibit the activation of the adenylate cyclase selectively and rapidly with agents acting to crosslink cell surface components, which may give a clue to the activation mechanism. The elaborate mechanisms of cell-cell communication occurring in D. discoideum are without precedent in biological literature, although models of oscillatory wave propagation have been proposed to account for pattern formation. Although it is unlikely that extracellular cAMP would be involved, it is not inconceivable that such mechanisms occur during the development of more evolutionarily advanced organisms. The organized communication system in D. discoideum is only apparent when cells are plated uniformly on a flat surface; such organized movements occurring in a three-dimensional structure such as an embryo would be very difficult to discern.
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PMID:Cell-cell interactions in the development of Dictyostelium. 285 27

Expression of the Dictyostelium discoideum pst-cath (CP2) gene is transcriptionally regulated during multicellular development, and the gene is inducible in competent single cells following administration of exogenous cAMP. The 5' flanking region of pst-cath (CP2) that extends from -313 to the Cap site (+1) has previously been shown to contain sufficient cis-acting regulatory elements for proper developmental and cAMP-inducible expression of a foreign gene [Datta and Firtel, 1987, Mol Cell Biol 7:149-159]. The -283 to -201 region includes two exceptional "G-boxes" centered at -233 and -217 respectively, and this approximately 80 bp region is essential for basal as well as regulated expression of the pst-cath (CP2) gene. Here we summarize results obtained from a detailed analysis of a series of linker-scanner mutants and mutants that carry small internal deletions within the essential 80-bp region. Insertion of a synthetic oligonucleotide that includes the downstream G-box is demonstrated to rescue a low level of cAMP-inducible expression following insertion into cassette mutants. The effect of introducing a change in the relative spacing between regulatory elements has also been investigated. We have analyzed nuclear extracts for the presence of DNA-binding proteins that interact specifically with the pst-cath (CP2) regulatory region and identified two such putative trans-acting factors: 1) the AT-factor that is observed within a few hours following the onset of starvation and that binds tightly to stretches of alternating adenine-thymine residues (poly(dA-dT]; and 2) the AG-factor that is present in nuclear extracts of aggregated cells. Competition studies have demonstrated significant differences in the affinity that characterizes the binding of the two factors to G-box-containing sequences. The binding specificities of these DNA-binding proteins have been analyzed using gel mobility-shift and DNaseI footprinting assays.
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PMID:Analysis of cis and trans elements involved in cAMP-inducible gene expression in Dictyostelium discoideum. 290 23


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