1887

Abstract

In the cAMP-dependent protein kinase A pathway antagonizes the cellular response to stress. It is shown here that the cellular content of Cdc25p, the upstream activator of Ras and adenylyl cyclase, decays upon various stresses such as heat shock and oxidative and ethanol shocks, whereas its phosphorylation level and its localization are unaffected. In parallel with the reduction of Cdc25p, the maximal capacity of the cell to accumulate cAMP decreases when its feedback regulation is abolished. A deletion of prevents this decrease. Paradoxically, in wild-type cells, with normal feedback regulation, the level of cAMP, which is much lower, is not reduced but is rather increased upon stress. These observations are consistent with a role of Cdc25p in sensing and transducing stress to downstream targets, either through a cAMP-independent pathway or by large fluctuations in the cAMP content of the cell.

Keyword(s): PKA, protein kinase A
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2004-10-01
2019-10-15
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References

  1. Boy-Marcotte, E., Perrot, M., Bussereau, F., Boucherie, H. & Jacquet, M. ( 1998; ). Msn2p and Msn4p control a large number of genes induced at the diauxic transition which are repressed by cyclic AMP in Saccharomyces cerevisiae. J Bacteriol 180, 1044–1052.
    [Google Scholar]
  2. Boy-Marcotte, E., Lagniel, G., Perrot, M., Bussereau, F., Boudsocq, A., Jacquet, M. & Labarre, J. ( 1999; ). The heat shock response in yeast: differential regulations and contributions of the Msn2p/Msn4p and Hsf1p regulons. Mol Microbiol 33, 274–283.[CrossRef]
    [Google Scholar]
  3. Camonis, J. H. & Jacquet, M. ( 1988; ). A new RAS mutation that suppresses the CDC25 gene requirement for growth of Saccharomyces cerevisiae. Mol Cell Biol 8, 2980–2983.
    [Google Scholar]
  4. Camonis, J. H., Kalekine, M., Gondre, B., Garreau, H., Boy-Marcotte, E. & Jacquet, M. ( 1986; ). Characterization, cloning and sequence analysis of the CDC25 gene which controls the cyclic AMP level of Saccharomyces cerevisiae. EMBO J 5, 375–380.
    [Google Scholar]
  5. Causton, H. C., Ren, B., Koh, S. S. & 7 other authors ( 2001; ). Remodeling of yeast genome expression in response to environmental changes. Mol Biol Cell 12, 323–337.[CrossRef]
    [Google Scholar]
  6. Cherkasova, V. A., McCully, R., Wang, Y., Hinnebusch, A. & Elion, E. A. ( 2003; ). A novel functional link between MAP kinase cascades and the Ras/cAMP pathway that regulates survival. Curr Biol 13, 1220–1226.[CrossRef]
    [Google Scholar]
  7. Colombo, S., Ma, P., Cauwenberg, L. & 8 other authors ( 1998; ). Involvement of distinct G-proteins, Gpa2 and Ras, in glucose- and intracellular acidification-induced cAMP signalling in the yeast Saccharomyces cerevisiae. EMBO J 17, 3326–3341.[CrossRef]
    [Google Scholar]
  8. Cook, J. G., Bardwell, L. & Thorner, J. ( 1997; ). Inhibitory and activating functions for MAPK Kss1 in the S. cerevisiae filamentous-growth signalling pathway. Nature 390, 85–88.[CrossRef]
    [Google Scholar]
  9. de Hoog, C. L., Koehler, J. A., Goldstein, M. D., Taylor, P., Figeys, D. & Moran, M. F. ( 2001; ). Ras binding triggers ubiquitination of the Ras exchange factor Ras-GRF2. Mol Cell Biol 21, 2107–2117.[CrossRef]
    [Google Scholar]
  10. Estruch, F. ( 2000; ). Stress-controlled transcription factors, stress-induced genes and stress tolerance in budding yeast. FEMS Microbiol Rev 24, 469–486.[CrossRef]
    [Google Scholar]
  11. Garreau, H., Geymonat, M., Renault, G. & Jacquet, M. ( 1996; ). Membrane-anchoring domains of Cdc25p, a Saccharomyces cerevisiae ras exchange factor. Biol Cell 86, 93–102.[CrossRef]
    [Google Scholar]
  12. Garreau, H., Hasan, R. N., Renault, G., Estruch, F., Boy-Marcotte, E. & Jacquet, M. ( 2000; ). Hyperphosphorylation of Msn2p and Msn4p in response to heat shock and the diauxic shift is inhibited by cAMP in Saccharomyces cerevisiae. Microbiology 146, 2113–2120.
    [Google Scholar]
  13. Gasch, A. P., Spellman, P. T., Kao, C. M., Carmel-Harel, O., Eisen, M. B., Storz, G., Botstein, D. & Brown, P. O. ( 2000; ). Genomic expression programs in the response of yeast cells to environmental changes. Mol Biol Cell 11, 4241–4257.[CrossRef]
    [Google Scholar]
  14. Geymonat, M., Wang, L., Garreau, H. & Jacquet, M. ( 1998; ). Ssa1p chaperone interacts with the guanine nucleotide exchange factor of ras Cdc25p and controls the cAMP pathway in Saccharomyces cerevisiae. Mol Microbiol 30, 855–864.[CrossRef]
    [Google Scholar]
  15. Ghaemmaghami, S., Huh, W. K., Bower, K., Howson, R. W., Belle, A., Dephoure, N., O'Shea, E. K. & Weissman, J. S. ( 2003; ). Global analysis of protein expression in yeast. Nature 425, 737–741.[CrossRef]
    [Google Scholar]
  16. Gorner, W., Durchschlag, E., Martinez-Pastor, M. T., Estruch, F., Ammerer, G., Hamilton, B., Ruis, H. & Schuller, C. ( 1998; ). Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity. Genes Dev 12, 586–597.[CrossRef]
    [Google Scholar]
  17. Gorner, W., Durchschlag, E., Wolf, J., Brown E. L., Ammerer, G., Ruis, H. & Schuller, C. ( 2002; ). Acute glucose starvation activates the nuclear localization signal of a stress-specific yeast transcription factor. EMBO J 21, 135–144.[CrossRef]
    [Google Scholar]
  18. Gross, E., Goldberg, D. & Levitzki, A. ( 1992a; ). Phosphorylation of the S. cerevisiae Cdc25 in response to glucose results in its dissociation from Ras. Nature 360, 762–765.[CrossRef]
    [Google Scholar]
  19. Gross, E., Marbach, I., Engelberg, D., Segal, M., Simchen, G. & Levitzki, A. ( 1992b; ). Anti-Cdc25 antibodies inhibit guanyl nucleotide-dependent adenylyl cyclase of Saccharomyces cerevisiae and cross-react with a 150-kilodalton mammalian protein. Mol Cell Biol 12, 2653–2661.
    [Google Scholar]
  20. Ho, J. & Bretscher, A. ( 2001; ). Ras regulates the polarity of the yeast actin cytoskeleton through the stress response pathway. Mol Biol Cell 12, 1541–1555.[CrossRef]
    [Google Scholar]
  21. Jacquet, M., Renault, G., Lallet, S., De Mey, J. & Goldbeter, A. ( 2003; ). Oscillatory nucleocytoplasmic shuttling of the general stress response transcriptional activators Msn2 and Msn4 in Saccharomyces cerevisiae. J Cell Biol 161, 497–505.[CrossRef]
    [Google Scholar]
  22. Jelinsky, S. A. & Samson, L. D. ( 1999; ). Global response of Saccharomyces cerevisiae to an alkylating agent. Proc Natl Acad Sci U S A 96, 1486–1491.[CrossRef]
    [Google Scholar]
  23. Kaplon, T. & Jacquet, M. ( 1995; ). The cellular content of Cdc25p, the Ras exchange factor in Saccharomyces cerevisiae, is regulated by destabilization through a cyclin destruction box. J Biol Chem 270, 20742–20747.[CrossRef]
    [Google Scholar]
  24. Martinez-Pastor, M. T., Marchler, G., Schuller, C., Marchler-Bauer, A., Ruis, H. & Estruch, F. ( 1996; ). The Saccharomyces cerevisiae zinc finger proteins Msn2p and Msn4p are required for transcriptional induction through the stress response element (STRE). EMBO J 15, 2227–2235.
    [Google Scholar]
  25. Muller, D., Exler, S., Aguilera-Vazquez, L., Guerrero-Martin, E. & Reuss, M. ( 2003; ). Cyclic AMP mediates the cell cycle dynamics of energy metabolism in Saccharomyces cerevisiae. Yeast 20, 351–367.[CrossRef]
    [Google Scholar]
  26. Nathan, D. F. & Lindquist, S. ( 1995; ). Mutational analysis of Hsp90 function: interactions with a steroid receptor and a protein kinase. Mol Cell Biol 15, 3917–3925.
    [Google Scholar]
  27. Nikawa, J., Sass, P. & Wigler, M. ( 1987a; ). Cloning and characterization of the low-affinity cyclic AMP phosphodiesterase gene of Saccharomyces cerevisiae. Mol Cell Biol 7, 3629–3636.
    [Google Scholar]
  28. Nikawa, J., Cameron, S., Toda, T., Ferguson, K. M. & Wigler, M. ( 1987b; ). Rigorous feedback control of cAMP levels in Saccharomyces cerevisiae. Genes Dev 1, 931–937.[CrossRef]
    [Google Scholar]
  29. Powers, S., Kataoka, T., Fasano, O., Goldfarb, M., Strathern, J. B., Broach, J. & Wigler, M. ( 1984; ). Genes in S. cerevisiae encoding proteins with domains homologous to the mammalian ras proteins. Cell 36, 607–612.[CrossRef]
    [Google Scholar]
  30. Rothstein, R. J. ( 1983; ). One-step gene disruption in yeast. Methods Enzymol 101, 202–211.
    [Google Scholar]
  31. Satroutdinov, A. D., Kuriyama, H. & Kobayashi, H. ( 1992; ). Oscillatory metabolism of Saccharomyces cerevisiae in continuous culture. FEMS Microbiol Lett 77, 261–267.
    [Google Scholar]
  32. Schmitt, A. P. & McEntee, K. ( 1996; ). Msn2p, a zinc finger DNA-binding protein, is the transcriptional activator of the multistress response in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A 93, 5777–5782.[CrossRef]
    [Google Scholar]
  33. Tanaka, K., Nakafuku, M., Satoh, T., Marshall, M. S., Gibbs, J. B., Matsumoto, K., Kaziro, Y. & Toh-e, A. ( 1990; ). S. cerevisiae genes IRA1 and IRA2 encode proteins that may be functionally equivalent to mammalian ras GTPase activating protein. Cell 60, 803–807.[CrossRef]
    [Google Scholar]
  34. Thevelein, J. M. & Beullens, M. ( 1985; ). Cyclic AMP and the stimulation of trehalase activity in the yeast Saccharomyces cerevisiae by carbon sources, nitrogen sources and inhibitors of protein synthesis. J Gen Microbiol 131, 3199–3209.
    [Google Scholar]
  35. Thevelein, J. M. & de Winde, J. H. ( 1999; ). Novel sensing mechanisms and targets for the cAMP-protein kinase A pathway in the yeast Saccharomyces cerevisiae. Mol Microbiol 33, 904–918.[CrossRef]
    [Google Scholar]
  36. Thevelein, J. M., Beullens, M., Honshoven, F., Hoebeeck, G., Detremerie, K., Griewel, B., den Hollander, J. A. & Jans, A. W. ( 1987; ). Regulation of the cAMP level in the yeast Saccharomyces cerevisiae: the glucose-induced cAMP signal is not mediated by a transient drop in the intracellular pH. J Gen Microbiol 133, 2197–2205.
    [Google Scholar]
  37. Thierry, A., Gaillon, L., Galibert, F. & Dujon, B. ( 1995; ). Construction of a complete genomic library of Saccharomyces cerevisiae and physical mapping of chromosome XI at 3·7 kb resolution. Yeast 11, 121–135.
    [Google Scholar]
  38. Toda, T., Uno, I., Ishikawa, T. & 7 other authors ( 1985; ). In yeast, RAS proteins are controlling elements of adenylate cyclase. Cell 40, 27–36.[CrossRef]
    [Google Scholar]
  39. Wach, A., Brachat, A., Pohlmann, R. & Philippsen, P. ( 1994; ). New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae. Yeast 10, 1793–1808.[CrossRef]
    [Google Scholar]
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