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. 1990 Sep;10(9):4518–4523. doi: 10.1128/mcb.10.9.4518

Glucose-induced hyperaccumulation of cyclic AMP and defective glucose repression in yeast strains with reduced activity of cyclic AMP-dependent protein kinase.

K Mbonyi 1, L van Aelst 1, J C Argüelles 1, A W Jans 1, J M Thevelein 1
PMCID: PMC361038  PMID: 2201893

Abstract

Addition of glucose or related fermentable sugars to derepressed cells of the yeast Saccharomyces cerevisiae triggers a RAS-mediated cyclic AMP (cAMP) signal that induces a protein phosphorylation cascade. In yeast mutants (tpk1w1, tpk2w1, and tpk3w1) containing reduced activity of cAMP-dependent protein kinase, fermentable sugars, as opposed to nonfermentable carbon sources, induced a permanent hyperaccumulation of cAMP. This finding confirms previous conclusions that fermentable sugars are specific stimulators of cAMP synthesis in yeast cells. Despite the huge cAMP levels present in these mutants, deletion of the gene (BCY1) coding for the regulatory subunit of cAMP-dependent protein kinase severely reduced hyperaccumulation of cAMP. Glucose-induced hyperaccumulation of cAMP was also observed in exponential-phase glucose-grown cells of the tpklw1 and tpk2w1 strains but not the tpk3w1 strain even though addition of glucose to glucose-repressed wild-type cells did not induce a cAMP signal. Investigation of mitochondrial respiration by in vivo 31P nuclear magnetic resonance spectroscopy showed the tpk1w1 and tpk2w1 strains, to be defective in glucose repression. These results are consistent with the idea that the signal transmission pathway from glucose to adenyl cyclase contains a glucose-repressible protein. They also show that a certain level of cAMP-dependent protein phosphorylation is required for glucose repression. Investigation of the glucose-induced cAMP signal and glucose-induced activation of trehalase in derepressed cells of strains containing only one of the wild-type TPK genes indicates that the transient nature of the cAMP signal is due to feedback inhibition by cAMP-dependent protein kinase.

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Beullens M., Mbonyi K., Geerts L., Gladines D., Detremerie K., Jans A. W., Thevelein J. M. Studies on the mechanism of the glucose-induced cAMP signal in glycolysis and glucose repression mutants of the yeast Saccharomyces cerevisiae. Eur J Biochem. 1988 Feb 15;172(1):227–231. doi: 10.1111/j.1432-1033.1988.tb13877.x. [DOI] [PubMed] [Google Scholar]
  2. Camonis J. H., Kalékine M., Gondré B., Garreau H., Boy-Marcotte E., Jacquet M. Characterization, cloning and sequence analysis of the CDC25 gene which controls the cyclic AMP level of Saccharomyces cerevisiae. EMBO J. 1986 Feb;5(2):375–380. doi: 10.1002/j.1460-2075.1986.tb04222.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Entian K. D. Genetic and biochemical evidence for hexokinase PII as a key enzyme involved in carbon catabolite repression in yeast. Mol Gen Genet. 1980;178(3):633–637. doi: 10.1007/BF00337871. [DOI] [PubMed] [Google Scholar]
  4. Goldstein A., Lampen J. O. Beta-D-fructofuranoside fructohydrolase from yeast. Methods Enzymol. 1975;42:504–511. doi: 10.1016/0076-6879(75)42159-0. [DOI] [PubMed] [Google Scholar]
  5. Herrero P., Fernández R., Moreno F. The hexokinase isoenzyme PII of Saccharomyces cerevisiae ia a protein kinase. J Gen Microbiol. 1989 May;135(5):1209–1216. doi: 10.1099/00221287-135-5-1209. [DOI] [PubMed] [Google Scholar]
  6. LOWRY O. H., ROSEBROUGH N. J., FARR A. L., RANDALL R. J. Protein measurement with the Folin phenol reagent. J Biol Chem. 1951 Nov;193(1):265–275. [PubMed] [Google Scholar]
  7. Ma H., Bloom L. M., Walsh C. T., Botstein D. The residual enzymatic phosphorylation activity of hexokinase II mutants is correlated with glucose repression in Saccharomyces cerevisiae. Mol Cell Biol. 1989 Dec;9(12):5643–5649. doi: 10.1128/mcb.9.12.5643. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Ma H., Bloom L. M., Zhu Z. M., Walsh C. T., Botstein D. Isolation and characterization of mutations in the HXK2 gene of Saccharomyces cerevisiae. Mol Cell Biol. 1989 Dec;9(12):5630–5642. doi: 10.1128/mcb.9.12.5630. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Mahler H. R., Jaynes P. K., McDonough J. P., Hanson D. K. Catabolite repression in yeast: mediation by cAMP. Curr Top Cell Regul. 1981;18:455–474. doi: 10.1016/b978-0-12-152818-8.50033-5. [DOI] [PubMed] [Google Scholar]
  10. Matsumoto K., Uno I., Toh-E A., Ishikawa T., Oshima Y. Cyclic AMP may not be involved in catabolite repression in Saccharomyes cerevisiae: evidence from mutants capable of utilizing it as an adenine source. J Bacteriol. 1982 Apr;150(1):277–285. doi: 10.1128/jb.150.1.277-285.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Mbonyi K., Beullens M., Detremerie K., Geerts L., Thevelein J. M. Requirement of one functional RAS gene and inability of an oncogenic ras variant to mediate the glucose-induced cyclic AMP signal in the yeast Saccharomyces cerevisiae. Mol Cell Biol. 1988 Aug;8(8):3051–3057. doi: 10.1128/mcb.8.8.3051. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Munder T., Küntzel H. Glucose-induced cAMP signaling in Saccharomyces cerevisiae is mediated by the CDC25 protein. FEBS Lett. 1989 Jan 2;242(2):341–345. doi: 10.1016/0014-5793(89)80498-3. [DOI] [PubMed] [Google Scholar]
  13. Nikawa J., Cameron S., Toda T., Ferguson K. M., Wigler M. Rigorous feedback control of cAMP levels in Saccharomyces cerevisiae. Genes Dev. 1987 Nov;1(9):931–937. doi: 10.1101/gad.1.9.931. [DOI] [PubMed] [Google Scholar]
  14. Thevelein J. M., Beullens M., Honshoven F., Hoebeeck G., Detremerie K., den Hollander J. A., Jans A. W. Regulation of the cAMP level in the yeast Saccharomyces cerevisiae: intracellular pH and the effect of membrane depolarizing compounds. J Gen Microbiol. 1987 Aug;133(8):2191–2196. doi: 10.1099/00221287-133-8-2191. [DOI] [PubMed] [Google Scholar]
  15. Toda T., Cameron S., Sass P., Zoller M., Wigler M. Three different genes in S. cerevisiae encode the catalytic subunits of the cAMP-dependent protein kinase. Cell. 1987 Jul 17;50(2):277–287. doi: 10.1016/0092-8674(87)90223-6. [DOI] [PubMed] [Google Scholar]
  16. Toda T., Uno I., Ishikawa T., Powers S., Kataoka T., Broek D., Cameron S., Broach J., Matsumoto K., Wigler M. In yeast, RAS proteins are controlling elements of adenylate cyclase. Cell. 1985 Jan;40(1):27–36. doi: 10.1016/0092-8674(85)90305-8. [DOI] [PubMed] [Google Scholar]
  17. Wigler M., Field J., Powers S., Broek D., Toda T., Cameron S., Nikawa J., Michaeli T., Colicelli J., Ferguson K. Studies of RAS function in the yeast Saccharomyces cerevisiae. Cold Spring Harb Symp Quant Biol. 1988;53(Pt 2):649–655. doi: 10.1101/sqb.1988.053.01.074. [DOI] [PubMed] [Google Scholar]

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