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Differential regulation of Tec1 by Fus3 and Kss1 confers signaling specificity in yeast development

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Abstract

Transcriptional regulation by mitogen-activated protein (MAP) kinase signaling cascades is a major control mechanism for eukaryotic development. In budding yeast, Fus3 and Kss1 are two MAP kinases that control two distinct developmental programs—mating and invasive growth. We investigated whether signal-specific activation of mating and invasive growth involves regulation of the transcription factor Tec1 by Fus3 and Kss1. We present evidence that, during mating, Fus3 phosphorylates Tec1 to downregulate this invasive growth-specific transcription factor and its target genes. This function of Fus3 is essential for correct execution of the mating program and is not shared by Kss1. We find that Kss1 controls the activity of Tec1 mainly during invasive growth by control of TEC1 gene expression. Our study suggests that signaling specificity can arise from differential regulation of a single transcription factor by two MAP kinases with shared functions in distinct developmental programs.

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References

  • Bardwell L, Cook JG, Voora D, Baggott DM, Martinez AR, Thorner J (1998) Repression of yeast Ste12 transcription factor by direct binding of unphosphorylated Kss1 MAPK and its regulation by the Ste7 MEK. Genes Dev 12:2887–2898

    CAS  PubMed  Google Scholar 

  • Bardwell AJ, Flatauer LJ, Matsukuma K, Thorner J, Bardwell L (2001) A conserved docking site in MEKs mediates high-affinity binding to MAP kinases and cooperates with a scaffold protein to enhance signal transmission. J Biol Chem 276:10374–10386

    Article  CAS  PubMed  Google Scholar 

  • Breitkreutz A, Tyers M (2002) MAPK signaling specificity: it takes two to tango. Trends Cell Biol 12:254–257

    Article  CAS  PubMed  Google Scholar 

  • Breitkreutz A, Boucher L, Tyers M (2001) MAPK specificity in the yeast pheromone response independent of transcriptional activation. Curr Biol 11:1266–1271

    Article  CAS  PubMed  Google Scholar 

  • Cook JG, Bardwell L, Kron SJ, Thorner J (1996) Two novel targets of the MAP kinase Kss1 are negative regulators of invasive growth in the yeast Saccharomyces cerevisiae. Genes Dev 10:2831–2848

    CAS  PubMed  Google Scholar 

  • Cook JG, Bardwell L, Thorner J (1997) Inhibitory and activating functions for MAPK Kss1 in the S. cerevisiae filamentous-growth signalling pathway. Nature 390:85–88

    Article  CAS  PubMed  Google Scholar 

  • Elion EA (2001) The Ste5p scaffold. J Cell Sci 114:3967–3978

    CAS  PubMed  Google Scholar 

  • Elion EA, Grisafi PL, Fink GR (1990) FUS3 encodes a cdc2+/CDC28-related kinase required for the transition from mitosis into conjugation. Cell 60:649–664

    Article  CAS  PubMed  Google Scholar 

  • Elion EA, Brill JA, Fink GR (1991) Functional redundancy in the yeast cell cycle: FUS3 and KSS1 have both overlapping and unique functions. Cold Spring Harb Symp Quant Biol 56:41–49

    CAS  PubMed  Google Scholar 

  • Elion EA, Satterberg B, Kranz JE (1993) FUS3 phosphorylates multiple components of the mating signal transduction cascade: evidence for STE12 and FAR1. Mol Biol Cell 4:495–510

    CAS  PubMed  Google Scholar 

  • Errede B, Ammerer G (1989) Ste12, a protein involved in cell-type-specific transcription and signal transduction in yeast, is part of protein–DNA complexes. Genes Dev 3:1349–1361

    CAS  PubMed  Google Scholar 

  • Esch RK, Errede B (2002) Pheromone induction promotes Ste11 degradation through a MAPK feedback and ubiquitin-dependent mechanism. Proc Natl Acad Sci USA 99:9160–9165

    Article  CAS  PubMed  Google Scholar 

  • Gartner A, Nasmyth K, Ammerer G (1992) Signal transduction in Saccharomyces cerevisiae requires tyrosine and threonine phosphorylation of FUS3 and KSS1. Genes Dev 6:1280–1292

    CAS  PubMed  Google Scholar 

  • Gavrias V, Andrianopoulos A, Gimeno CJ, Timberlake WE (1996) Saccharomyces cerevisiae TEC1 is required for pseudohyphal growth. Mol Microbiol 19:1255–1263

    CAS  PubMed  Google Scholar 

  • Gustin MC, Albertyn J, Alexander M, Davenport K (1998) MAP kinase pathways in the yeast Saccharomyces cerevisiae. Microbiol Mol Biol Rev 62:1264–1300

    CAS  PubMed  Google Scholar 

  • Guthrie C, Fink GR (1991) Guide to yeast genetics and molecular biology. Methods Enzymol 194

  • Han J, Jiang Y, Li Z, Kravchenko VV, Ulevitch RJ (1997) Activation of the transcription factor MEF2C by the MAP kinase p38 in inflammation. Nature 386:296–299

    Article  CAS  PubMed  Google Scholar 

  • Ho Y, et al (2002) Systematic identification of protein complexes in Saccharomyces cerevisiae by mass spectrometry. Nature 415:180–183

    Article  Google Scholar 

  • Holstege FC, et al (1998) Dissecting the regulatory circuitry of a eukaryotic genome. Cell 95:717–728

    Article  CAS  PubMed  Google Scholar 

  • Kato Y, Kravchenko VV, Tapping RI, Han J, Ulevitch RJ, Lee JD (1997) BMK1/ERK5 regulates serum-induced early gene expression through transcription factor MEF2C. EMBO J 16:7054–7066

    Article  CAS  PubMed  Google Scholar 

  • Köhler T, Wesche S, Taheri N, Braus GH, Mösch H-U (2002) Dual role of the Saccharomyces cerevisiae TEA/ATTS family transcription factor Tec1p in regulation of gene expression and cellular development. Eukaryot Cell 1:673–686

    Article  PubMed  Google Scholar 

  • Lange CA, Shen T, Horwitz KB (2000) Phosphorylation of human progesterone receptors at serine-294 by mitogen-activated protein kinase signals their degradation by the 26S proteasome. Proc Natl Acad Sci USA 97:1032–1037

    Article  CAS  PubMed  Google Scholar 

  • Lo WS, Dranginis AM (1998) The cell surface flocculin Flo11 is required for pseudohyphae formation and invasion by Saccharomyces cerevisiae. Mol Biol Cell 9:161–171

    CAS  PubMed  Google Scholar 

  • Madhani HD, Fink GR (1997) Combinatorial control required for the specificity of yeast MAPK signaling. Science 275:1314–1317

    Article  CAS  PubMed  Google Scholar 

  • Madhani HD, Fink GR (1998) The riddle of MAP kinase signaling specificity. Trends Genet 14:151–155

    Article  CAS  PubMed  Google Scholar 

  • Madhani HD, Styles CA, Fink GR (1997) MAP kinases with distinct inhibitory functions impart signaling specificity during yeast differentiation. Cell 91:673–684

    Article  CAS  PubMed  Google Scholar 

  • Madhani HD, Galitski T, Lander ES, Fink GR (1999) Effectors of a developmental mitogen-activated protein kinase cascade revealed by expression signatures of signaling mutants. Proc Natl Acad Sci USA 96:12530–12535

    Article  CAS  PubMed  Google Scholar 

  • Metodiev MV, Matheos D, Rose MD, Stone DE (2002) Regulation of MAPK function by direct interaction with the mating-specific G-alpha in yeast. Science 296:1483–1486

    Article  CAS  PubMed  Google Scholar 

  • Mösch H-U, Fink GR (1997) Dissection of filamentous growth by transposon mutagenesis in Saccharomyces cerevisiae. Genetics 145:671–684

    PubMed  Google Scholar 

  • Oehlen L, Cross FR (1998) The mating factor response pathway regulates transcription of TEC1, a gene involved in pseudohyphal differentiation of Saccharomyces cerevisiae. FEBS Lett 429:83–88

    Article  CAS  PubMed  Google Scholar 

  • Peter M, Gartner A, Horecka J, Ammerer G, Herskowitz I (1993) FAR1 links the signal transduction pathway to the cell cycle machinery in yeast. Cell 73:747–760

    Article  CAS  PubMed  Google Scholar 

  • Roberts CJ et al (2000) Signaling and circuitry of multiple MAPK pathways revealed by a matrix of global gene expression profiles. Science 287:873–880

    Article  CAS  PubMed  Google Scholar 

  • Roberts RL, Fink GR (1994) 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 8:2974–2985

    CAS  PubMed  Google Scholar 

  • Sabbagh W Jr, Flatauer LJ, Bardwell AJ, Bardwell L (2001) Specificity of MAP kinase signaling in yeast differentiation involves transient versus sustained MAPK activation. Mol Cell 8:683–691

    Article  CAS  PubMed  Google Scholar 

  • Schaeffer HJ, Weber MJ (1999) Mitogen-activated protein kinases: specific messages from ubiquitous messengers. Mol Cell Biol 19:2435–2444

    CAS  PubMed  Google Scholar 

  • Schlenstedt G, Saavedra C, Loeb JD, Cole CN, Silver PA (1995) The GTP-bound form of the yeast Ran/TC4 homologue blocks nuclear protein import and appearance of poly(A)+ RNA in the cytoplasm. Proc Natl Acad Sci USA 92:225–229

    CAS  PubMed  Google Scholar 

  • Sharrocks AD, Yang SH, Galanis A (2000) Docking domains and substrate-specificity determination for MAP kinases. Trends Biochem Sci 25:448–453

    Article  CAS  PubMed  Google Scholar 

  • Song D, Dolan JW, Yuan YL, Fields S (1991) Pheromone-dependent phosphorylation of the yeast STE12 protein correlates with transcriptional activation. Genes Dev 5:741–750

    CAS  PubMed  Google Scholar 

  • Stronach BE, Perrimon N (1999) Stress signaling in Drosophila. Oncogene 18:6172–6182

    Article  CAS  PubMed  Google Scholar 

  • Taheri N, Köhler T, Braus GH, Mösch H-U (2000) Asymmetrically localized Bud8p and Bud9p proteins control yeast cell polarity and development. EMBO J 19:6686–6696

    Article  CAS  PubMed  Google Scholar 

  • Tan PB, Kim SK (1999) Signaling specificity: the RTK/RAS/MAP kinase pathway in metazoans. Trends Genet 15:145–149

    Article  CAS  PubMed  Google Scholar 

  • Tedford K, Kim S, Sa D, Stevens K, Tyers M (1997) Regulation of the mating pheromone and invasive growth responses in yeast by two MAP kinase substrates. Curr Biol 7:228–238

    Article  CAS  PubMed  Google Scholar 

  • Vaudry D, Stork PJ, Lazarovici P, Eiden LE (2002) Signaling pathways for PC12 cell differentiation: making the right connections. Science 296:1648–1649

    Article  CAS  PubMed  Google Scholar 

  • Widmann C, Gibson S, Jarpe MB, Johnson GL (1999) Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev 79:143–180

    CAS  PubMed  Google Scholar 

  • Yang SH, Sharrocks AD, Whitmarsh AJ (2003) Transcriptional regulation by the MAP kinase signaling cascades. Gene 320:3–21

    Article  CAS  PubMed  Google Scholar 

  • Zeitlinger J, et al (2003) Program-specific distribution of a transcription factor dependent on partner transcription factor and MAPK signaling. Cell 113:395–404

    Article  CAS  PubMed  Google Scholar 

Download references

Acknowledgements

We thank Ashton Breitkreutz, Gerald Fink, Hiten Madhani, Markus Rudolph, and Mike Tyers for generous gifts of reagents. We are grateful to Maria Meyer for excellent technical assistance. This work was supported by grants from the Deutsche Forschungsgemeinschaft and the Volkwagenstiftung.

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Correspondence to Hans-Ulrich Mösch.

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Communicated by S. Hohmann

The first two authors have equally contributed to this work

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Brückner, S., Köhler, T., Braus, G.H. et al. Differential regulation of Tec1 by Fus3 and Kss1 confers signaling specificity in yeast development. Curr Genet 46, 331–342 (2004). https://doi.org/10.1007/s00294-004-0545-1

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