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Query: UMLS:C0038187 (starvation)
 24,951 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

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

We have isolated a snf1/ccr1 mutant of Saccharomyces cerevisiae which loses viability upon starvation and fails to accumulate glycogen in response to abrupt depletion of phosphate or glucose. A snf1 null mutant is sensitive to heat stress and starvation and fails to accumulate glycogen during growth in rich medium. The phenotypes of the snf1 mutants are those commonly associated with an overactivation of the adenylate cyclase pathway. Mutations in adenylate cyclase or RAS2 which decrease the level of cAMP in the cell moderate the snf1 phenotype. In contrast, a mutation in RAS2 (RAS2val19) which increases the level of cAMP or a mutation in the regulatory subunit (BCY1) of cAMP-dependent protein kinase which results in unregulated cAMP-dependent protein kinase activity accentuates the snf1 phenotype. However, the action of SNF1 in the stress response appears at least partly independent of cAMP-dependent protein kinase because a snf1 phenotype is observed in a strain that lacks all three of the genes that encode the catalytic subunits of cAMP-dependent protein kinase. SNF1 therefore acts at least in part through a cAMP-independent pathway.
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PMID:Deletion of SNF1 affects the nutrient response of yeast and resembles mutations which activate the adenylate cyclase pathway. 175 15

Two Dictyostelium discoideum protein kinase(PK)-encoding cDNAs (Dd PK1 and Dd PK2) have been isolated by hybridization with an oligodeoxyribonucleotide derived from a highly conserved region of eukaryotic PKs. The two nucleotide (nt) sequences encode new putative serine/threonine-specific PKs. Dd PK1 is a partial cDNA covering the entire catalytic domain. The derived amino acid (aa) sequence is about 30% identical to both cAMP-dependent protein kinase (cAPK) and protein kinase C. The Dd PK2 sequence was extended through the isolation of a genomic fragment encoding a complete putative protein. A single intron is present, as deduced from sequence comparison with the cDNA. The catalytic domain appears more closely related to the catalytic subunit of cAPK (54% sequence identity). However, our nt sequence potentially codes for a much larger protein (648 vs. about 350 aa for most cAPKs) with a N-terminal half containing long homopolymers of threonines, glutamines and asparagines. Similar repeats occur at the C terminus of Dd PK1, Dd PK1 is expressed in vegetatively growing cells and during development. Dd PK1 RNA decreases after 6 h of starvation to re-accumulate once the cells have aggregated. Dd PK2 transcripts, present at a low amount in growing cells, rise upon starvation. A switch to a shorter form of transcripts occurs between 3 and 6 h into development.
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PMID:Isolation of two genes encoding putative protein kinases regulated during Dictyostelium discoideum development. 186 10

Ten spontaneous and four in vitro constructed mutations in the gene encoding the regulatory subunit of cAMP-dependent protein kinase of Saccharomyces cerevisiae display very different phenotypes. The DNA nucleotide sequence of each spontaneous mutation was determined. Mutations were found in both the cAMP-binding domains and proximal to the cAMP-dependent protein kinase phosphorylation site. The latter mutations exhibited dominant traits when gene dosage was increased. The variation of phenotypes of sra1 mutations was examined. Many aspects of growth are affected, including growth on nonfermentable carbon sources, accumulation of glycogen, ability to sporulate, and ability to survive starvation. The null mutations affect all these traits. None of the spontaneous mutations confer the null phenotype. Instead, these mutations can be placed into groups of increasing severity based on the number of traits affected. These traits reflect the functions of the cAMP-dependent protein kinase substrates and ranking of sra1 phenotypes probably reflects a progressive defect in one or more aspects of the regulatory subunit function.
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PMID:Yeast cAMP-dependent protein kinase regulatory subunit mutations display a variety of phenotypes. 216 21

Entry into meiosis in Saccharomyces cerevisiae cells is regulated by starvation through the adenylate cyclase/cAMP-dependent protein kinase (AC/PK) pathway. The gene IME1 is also involved in starvation control of meiosis. Multicopy IME1 plasmids overcome the meiotic deficiency of bcy1 and of RASval19 diploids. Double mutants ime1 cdc25 and ime1 ras2 are sporulation deficient. These results suggest that IME1 comes after the AC/PK cascade. Furthermore, the level of IME1 transcripts is affected by mutations in the AC/PK genes CDC25, CYR1 and BCY1. Moreover, the addition of cAMP to a cyr1-2 diploid suppresses IME1 transcription. The presence in a bcy1 diploid of IME1 multicopy plasmids does not cure the failure of bcy1 cells to arrest as unbudded cells following starvation and to enter the G0 state (thermotolerance, synthesis of unique G0 proteins). This indicates that the pathway downstream of the AC/PK cascade branches to control meiosis through IME1, and to control entry into G0 and cell cycle initiation, independently of IME1.
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PMID:The adenylate cyclase/protein kinase cascade regulates entry into meiosis in Saccharomyces cerevisiae through the gene IME1. 220 44

The yeast Saccharomyces cerevisiae contains two functionally redundant genes RAS1 and RAS2, which are homologous to the mammalian ras gene family and are required for vegetative growth. We isolated and characterized five temperature-sensitive alleles of RAS2. In a ras1 strain, these alleles cause growth arrest at the G1 stage of the cell cycle. Revertants capable of growth at the nonpermissive temperature define four recessive, extragenic complementation groups. Suppressors in one complementation group (designated yak1) are particularly intriguing because they appear to alleviate only the growth defect of the temperature-sensitive ras mutants and do not show any of the phenotypes, such as heat shock sensitivity or starvation sensitivity, associated with increased production of cAMP. The YAK1 gene has been cloned, and disruptions generated in vitro reveal that it is not essential for growth and that its loss confers growth to a strain deleted for tpk1, tpk2, and tpk3, the structural genes for the catalytic subunit of the cAMP-dependent protein kinase. These results place Yak1 downstream from, or on a parallel pathway to, the kinase step in the Ras/cAMP pathway. Finally, the coding region predicts a protein with significant homology to the family of protein kinases, suggesting that loss of cAMP-dependent protein kinase function can be suppressed by the loss of a second protein kinase.
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PMID:Loss of Ras activity in Saccharomyces cerevisiae is suppressed by disruptions of a new kinase gene, YAKI, whose product may act downstream of the cAMP-dependent protein kinase. 255 53

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

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

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

We undertook a study to define the role of cyclic AMP [cAMP] in modulating the secretion of transcobalamin II (TC-II) in the mouse macrophage like cell line J774. J774 was observed to secrete large amounts of TC-II, particularly in the presence of 8-bromo cAMP or cholera toxin or when grown in medium supplemented with low concentrations of horse serum (1% or 5%) or in serum-free medium. Variant cell lines derived from J774 and deficient either in adenylate cyclase (ac -) or cAMP-dependent protein kinase (pk -) activity showed very low and intermediate levels of basal secretory activity of TC-II, respectively, compared to J774. Maximum secretory activity of TC-II was observed in J774 under conditions in which growth was poorest (in the presence of 8-bromo-cAMP or 1% or 5% horse serum-supplemented medium or in serum-free medium). Cells grown in serum-free medium were found to have elevated basal adenylate cyclase activity and cAMP levels compared to those grown in medium supplemented with 20% horse serum. The data from this study demonstrate a negative correlation between growth activity and TC-II secretion in the J774 cell line. The stimulatory effect of exogenous cAMP on TC-II secretion by J774, the reduced secretory activity of the variant lines ac- and pk- and the observed increase in cell cAMP levels under conditions of serum starvation in which TC-II secretion is considerably enhanced, suggest that cell cAMP is an important modulator of TC-II secretion and growth behavior in the J774 cell line.
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PMID:The modulation of transcobalamin II (TC-II) production by cyclic adenosine 3',5'-monophosphate in the murine macrophage cell line J774: relationship to growth behavior. 300 44


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