Skip to main content
The EMBO Journal logoLink to The EMBO Journal
. 1999 Mar 1;18(5):1257–1269. doi: 10.1093/emboj/18.5.1257

MAP kinase and cAMP filamentation signaling pathways converge on the unusually large promoter of the yeast FLO11 gene.

S Rupp 1, E Summers 1, H J Lo 1, H Madhani 1, G Fink 1
PMCID: PMC1171216  PMID: 10064592

Abstract

In Saccharomyces cerevisiae, two major signal transduction pathways, the Kss1 MAPK pathway and the cAMP-regulated pathway, are critical for the differentiation of round yeast form cells to multicellular, invasive pseudohyphae. Here we report that these parallel pathways converge on the promoter of a gene, FLO11, which encodes a cell surface protein required for pseudohyphal formation. The FLO11 promoter is unusually large, containing at least four upstream activation sequences (UASs) and nine repression elements which together span at least 2.8 kb. Several lines of evidence indicate that the MAPK and cAMP signals are received by distinct transcription factors and promoter elements. First, regulation via the MAPK pathway requires the transcription factors Ste12p/Tec1p, whereas cAMP-mediated activation requires a distinct factor, Flo8p. Secondly, mutations in either pathway block FLO11 transcription. Overexpression of STE12 can suppress the loss of FLO8, and overexpression of FLO8 can suppress the loss of STE12. Finally, multiple distinct promoter regions of the FLO11 promoter are required for its activation by either Flo8p or Ste12p/ Tec1p. Thus, like the promoters of the key developmental genes, HO and IME1, the FLO11 promoter is large and complex, endowing it with the ability to integrate multiple inputs.

Full Text

The Full Text of this article is available as a PDF (419.2 KB).

Selected References

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

  1. Alspaugh J. A., Perfect J. R., Heitman J. Cryptococcus neoformans mating and virulence are regulated by the G-protein alpha subunit GPA1 and cAMP. Genes Dev. 1997 Dec 1;11(23):3206–3217. doi: 10.1101/gad.11.23.3206. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Christianson T. W., Sikorski R. S., Dante M., Shero J. H., Hieter P. Multifunctional yeast high-copy-number shuttle vectors. Gene. 1992 Jan 2;110(1):119–122. doi: 10.1016/0378-1119(92)90454-w. [DOI] [PubMed] [Google Scholar]
  3. Dürrenberger F., Wong K., Kronstad J. W. Identification of a cAMP-dependent protein kinase catalytic subunit required for virulence and morphogenesis in Ustilago maydis. Proc Natl Acad Sci U S A. 1998 May 12;95(10):5684–5689. doi: 10.1073/pnas.95.10.5684. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Gimeno C. J., Ljungdahl P. O., Styles C. A., Fink G. R. Unipolar cell divisions in the yeast S. cerevisiae lead to filamentous growth: regulation by starvation and RAS. Cell. 1992 Mar 20;68(6):1077–1090. doi: 10.1016/0092-8674(92)90079-r. [DOI] [PubMed] [Google Scholar]
  5. Gold S., Duncan G., Barrett K., Kronstad J. cAMP regulates morphogenesis in the fungal pathogen Ustilago maydis. Genes Dev. 1994 Dec 1;8(23):2805–2816. doi: 10.1101/gad.8.23.2805. [DOI] [PubMed] [Google Scholar]
  6. Golemis E. A., Brent R. Fused protein domains inhibit DNA binding by LexA. Mol Cell Biol. 1992 Jul;12(7):3006–3014. doi: 10.1128/mcb.12.7.3006. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Guarente L., Ptashne M. Fusion of Escherichia coli lacZ to the cytochrome c gene of Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1981 Apr;78(4):2199–2203. doi: 10.1073/pnas.78.4.2199. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Kobayashi O., Suda H., Ohtani T., Sone H. Molecular cloning and analysis of the dominant flocculation gene FLO8 from Saccharomyces cerevisiae. Mol Gen Genet. 1996 Jul 26;251(6):707–715. doi: 10.1007/BF02174120. [DOI] [PubMed] [Google Scholar]
  9. Kübler E., Mösch H. U., Rupp S., Lisanti M. P. Gpa2p, a G-protein alpha-subunit, regulates growth and pseudohyphal development in Saccharomyces cerevisiae via a cAMP-dependent mechanism. J Biol Chem. 1997 Aug 15;272(33):20321–20323. doi: 10.1074/jbc.272.33.20321. [DOI] [PubMed] [Google Scholar]
  10. Lambrechts M. G., Bauer F. F., Marmur J., Pretorius I. S. Muc1, a mucin-like protein that is regulated by Mss10, is critical for pseudohyphal differentiation in yeast. Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8419–8424. doi: 10.1073/pnas.93.16.8419. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. Lambrechts M. G., Pretorius I. S., D'Aguanno V. S., Sollitti P., Marmur J. Multiple positive and negative cis-acting elements of the STA2 gene regulate glucoamylase synthesis in Saccharomyces cerevisiae. Gene. 1994 Sep 2;146(2):137–144. doi: 10.1016/0378-1119(94)90286-0. [DOI] [PubMed] [Google Scholar]
  12. Liu H., Styles C. A., Fink G. R. Elements of the yeast pheromone response pathway required for filamentous growth of diploids. Science. 1993 Dec 10;262(5140):1741–1744. doi: 10.1126/science.8259520. [DOI] [PubMed] [Google Scholar]
  13. Liu H., Styles C. A., Fink G. R. Saccharomyces cerevisiae S288C has a mutation in FLO8, a gene required for filamentous growth. Genetics. 1996 Nov;144(3):967–978. doi: 10.1093/genetics/144.3.967. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Lo H. J., Köhler J. R., DiDomenico B., Loebenberg D., Cacciapuoti A., Fink G. R. Nonfilamentous C. albicans mutants are avirulent. Cell. 1997 Sep 5;90(5):939–949. doi: 10.1016/s0092-8674(00)80358-x. [DOI] [PubMed] [Google Scholar]
  15. Lo W. S., Dranginis A. M. FLO11, a yeast gene related to the STA genes, encodes a novel cell surface flocculin. J Bacteriol. 1996 Dec;178(24):7144–7151. doi: 10.1128/jb.178.24.7144-7151.1996. [DOI] [PMC free article] [PubMed] [Google Scholar]
  16. Lo W. S., Dranginis A. M. The cell surface flocculin Flo11 is required for pseudohyphae formation and invasion by Saccharomyces cerevisiae. Mol Biol Cell. 1998 Jan;9(1):161–171. doi: 10.1091/mbc.9.1.161. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Lorenz M. C., Heitman J. Yeast pseudohyphal growth is regulated by GPA2, a G protein alpha homolog. EMBO J. 1997 Dec 1;16(23):7008–7018. doi: 10.1093/emboj/16.23.7008. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Madhani H. D., Fink G. R. The control of filamentous differentiation and virulence in fungi. Trends Cell Biol. 1998 Sep;8(9):348–353. doi: 10.1016/s0962-8924(98)01298-7. [DOI] [PubMed] [Google Scholar]
  19. Madhani H. D., Styles C. A., Fink G. R. MAP kinases with distinct inhibitory functions impart signaling specificity during yeast differentiation. Cell. 1997 Nov 28;91(5):673–684. doi: 10.1016/s0092-8674(00)80454-7. [DOI] [PubMed] [Google Scholar]
  20. Myers A. M., Tzagoloff A., Kinney D. M., Lusty C. J. Yeast shuttle and integrative vectors with multiple cloning sites suitable for construction of lacZ fusions. Gene. 1986;45(3):299–310. doi: 10.1016/0378-1119(86)90028-4. [DOI] [PubMed] [Google Scholar]
  21. Mösch H. U., Fink G. R. Dissection of filamentous growth by transposon mutagenesis in Saccharomyces cerevisiae. Genetics. 1997 Mar;145(3):671–684. doi: 10.1093/genetics/145.3.671. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Mösch H. U., Roberts R. L., Fink G. R. Ras2 signals via the Cdc42/Ste20/mitogen-activated protein kinase module to induce filamentous growth in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5352–5356. doi: 10.1073/pnas.93.11.5352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Nikawa J., Sass P., Wigler M. Cloning and characterization of the low-affinity cyclic AMP phosphodiesterase gene of Saccharomyces cerevisiae. Mol Cell Biol. 1987 Oct;7(10):3629–3636. doi: 10.1128/mcb.7.10.3629. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Olivas W. M., Muhlrad D., Parker R. Analysis of the yeast genome: identification of new non-coding and small ORF-containing RNAs. Nucleic Acids Res. 1997 Nov 15;25(22):4619–4625. doi: 10.1093/nar/25.22.4619. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Roberts R. L., Fink G. R. Elements of a single MAP kinase cascade in Saccharomyces cerevisiae mediate two developmental programs in the same cell type: mating and invasive growth. Genes Dev. 1994 Dec 15;8(24):2974–2985. doi: 10.1101/gad.8.24.2974. [DOI] [PubMed] [Google Scholar]
  26. Robertson L. S., Fink G. R. The three yeast A kinases have specific signaling functions in pseudohyphal growth. Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13783–13787. doi: 10.1073/pnas.95.23.13783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Sikorski R. S., Hieter P. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae. Genetics. 1989 May;122(1):19–27. doi: 10.1093/genetics/122.1.19. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Tanaka K., Matsumoto K., Toh-E A. IRA1, an inhibitory regulator of the RAS-cyclic AMP pathway in Saccharomyces cerevisiae. Mol Cell Biol. 1989 Feb;9(2):757–768. doi: 10.1128/mcb.9.2.757. [DOI] [PMC free article] [PubMed] [Google Scholar]
  29. Teunissen A. W., Steensma H. Y. Review: the dominant flocculation genes of Saccharomyces cerevisiae constitute a new subtelomeric gene family. Yeast. 1995 Sep 15;11(11):1001–1013. doi: 10.1002/yea.320111102. [DOI] [PubMed] [Google Scholar]
  30. Thanos D., Maniatis T. Virus induction of human IFN beta gene expression requires the assembly of an enhanceosome. Cell. 1995 Dec 29;83(7):1091–1100. doi: 10.1016/0092-8674(95)90136-1. [DOI] [PubMed] [Google Scholar]
  31. 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]
  32. 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]
  33. Vivier M. A., Pretorius I. S. Identification of a functional TATA element in the STA2 glucoamylase gene promoter from Saccharomyces cerevisiae. Curr Genet. 1998 Jan;33(1):10–15. doi: 10.1007/s002940050302. [DOI] [PubMed] [Google Scholar]
  34. Ward M. P., Gimeno C. J., Fink G. R., Garrett S. SOK2 may regulate cyclic AMP-dependent protein kinase-stimulated growth and pseudohyphal development by repressing transcription. Mol Cell Biol. 1995 Dec;15(12):6854–6863. doi: 10.1128/mcb.15.12.6854. [DOI] [PMC free article] [PubMed] [Google Scholar]
  35. Xu J. R., Hamer J. E. MAP kinase and cAMP signaling regulate infection structure formation and pathogenic growth in the rice blast fungus Magnaporthe grisea. Genes Dev. 1996 Nov 1;10(21):2696–2706. doi: 10.1101/gad.10.21.2696. [DOI] [PubMed] [Google Scholar]

Articles from The EMBO Journal are provided here courtesy of Nature Publishing Group

RESOURCES