Abstract
The filamentous/invasive growth pathway is activated by nutrient limitation in the haploid form of the yeast Saccharomyces cerevisiae, whereas exposure to mating-pheromone causes cells to differentiate into gametes. Although these two pathways respond to very different stimuli and generate very different responses, they utilize many of the same signaling components. This implies the need for robust mechanisms to maintain signal fidelity. Dse1 was identified in an allele-specific suppressor screen for proteins that interact with the pheromone-responsive Gβγ, and found to bind both to a Gβγ-affinity column, and to the shared MEKK, Ste11. Although overexpression of Dse1 stimulated invasive growth and transcription of both filamentation and mating-specific transcriptional reporters, deletion of DSE1 had no effect on these outputs. In contrast, pheromone hyper-induced transcription of the filamentation reporter in cells lacking Dse1 and in cells expressing a mutant form of Gβ that exhibits diminished interaction with Dse1. Thus, the interaction of Dse1 with both Gβ and Ste11 may be designed to control cross talk between the pheromone and filamentation pathways.
Similar content being viewed by others
References
Ausubel FM, Brent R, Kingston RE, Moore DD, Seidman JG, Smith JA, Struhl K (1994) Protocols in molecular biology. Wiley, New York
Bar EE, Ellicott AT, Stone DE (2003) Gβγ recruits Rho1 to the site of polarized growth during mating in budding yeast. J Biol Chem 278:21798–21804
Bardwell L (2004) A walk-through of the yeast mating pheromone response pathway. Peptides 25:1465–1476
Caldwell GA, Naider F, Becker JM (1995) Fungal lipopeptide mating pheromones: a model system for the study of protein prenylation. Microbiol Rev 59:406–422
Caponigro G, Abedi MR, Hurlburt AP, Maxfield A, Judd W, Kamb A (1998) Transdominant genetic analysis of a growth control pathway. Proc Natl Acad Sci USA 95:7508–7513
Choi KY, Satterberg B, Lyons DM, Elion EA (1994) Ste5 tethers multiple protein kinases in the MAP kinase cascade required for mating in S. cerevisiae. Cell 78:499–512
Cismowski MJ, Metodiev M, Draper E, Stone DE (2001) Biochemical analysis of yeast Gα mutants that enhance adaptation to pheromone. Biochem Biophys Res Commun 284:247–254
Cole GM, Stone DE, Reed SI (1990) Stoichiometry of G protein subunits affects the Saccharomyces cerevisiae mating pheromone signal transduction pathway. Mol Cell Biol 10:510–517
Colman-Lerner A, Chin TE, Brent R (2001) Yeast Cbk1 and Mob2 activate daughter-specific genetic programs to induce asymmetric cell fates. Cell 107:739–750
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
Doolin MT, Johnson AL, Johnston LH, Butler G (2001) Overlapping and distinct roles of the duplicated yeast transcription factors Ace2p and Swi5p. Mol Microbiol 40:422–432
Drogen F, O’Rourke SM, Stucke VM, Jaquenoud M, Neiman AM, Peter M (2000) Phosphorylation of the MEKK Ste11p by the PAK-like kinase Ste20p is required for MAP kinase signaling in vivo. Curr Biol 10:630–639
Elion EA (2000) Pheromone response, mating and cell biology. Curr Opin Microbiol 3:573–581
Elion EA (2001) The Ste5p scaffold. J Cell Sci 114:3967–3978
Flatauer LJ, Zadeh SF, Bardwell L (2005) Mitogen-activated protein kinases with distinct requirements for Ste5 scaffolding influence signaling specificity in Saccharomyces cerevisiae. Mol Cell Biol 25:1793–1803
Frydlova I, Malcova I, Vasicova P, Hasek J (2009) Deregulation of DSE1 gene expression results in aberrant budding within the birth scar and cell wall integrity pathway activation in Saccharomyces cerevisiae. Eukaryot Cell 8:586–594
Fuller RS, Sterne RE, Thorner J (1988) Enzymes required for yeast prohormone processing. Annu Rev Physiol 50:345–362
Gietz D, St Jean A, Woods RA, Schiestl RH (1992) Improved method for high efficiency transformation of intact yeast cells. Nucleic Acids Res 20:1425
Gimeno CJ, Ljungdahl PO, Styles CA, Fink GR (1992) Unipolar cell divisions in the yeast S. cerevisiae lead to filamentous growth: regulation by starvation and RAS. Cell 68:1077–1090
Gustin MC, Albertyn J, Alexander M, Davenport K (1998) MAP kinase pathways in the yeast Saccharomyces cerevisiae. Microbiol Mol Biol Rev 62:1264–1300
Hagen DC, McCaffrey G, Sprague GF Jr (1986) Evidence the yeast STE3 gene encodes a receptor for the peptide pheromone a factor: gene sequence and implications for the structure of the presumed receptor. Proc Natl Acad Sci USA 83:1418–1422
Harris K et al (2001) Role of scaffolds in MAP kinase pathway specificity revealed by custom design of pathway-dedicated signaling proteins. Curr Biol 11:1815–1824
Huh WK et al (2003) Global analysis of protein localization in budding yeast. Nature 425:686–691
Ito H, Fukuda Y, Murata K, Kimura A (1983) Transformation of intact yeast cells treated with alkali cations. J Bacteriol 153:163–168
King L, Butler G (1998) Ace2p, a regulator of CTS1 (chitinase) expression, affects pseudohyphal production in Saccharomyces cerevisiae. Curr Genet 34:183–191
Kovacech B, Nasmyth K, Schuster T (1996) EGT2 gene transcription is induced predominantly by Swi5 in early G1. Mol Cell Biol 16:3264–3274
Kron SJ, Gow NA (1995) Budding yeast morphogenesis: signalling, cytoskeleton and cell cycle. Curr Opin Cell Biol 7:845–855
Kron SJ, Styles CA, Fink GR (1994) Symmetric cell division in pseudohyphae of the yeast Saccharomyces cerevisiae. Mol Biol Cell 5:1003–1022
Lamson RE, Winters MJ, Pryciak PM (2002) Cdc42 regulation of kinase activity and signaling by the yeast p21-activated kinase Ste20. Mol Cell Biol 22:2939–2951
Li E, Meldrum E, Stratton HF, Stone DE (1998) Substitutions in the pheromone-responsive Gβ protein of Saccharomyces cerevisiae confer a defect in recovery from pheromone treatment. Genetics 148:947–961
Mackay V, Manney TR (1974) Mutations affecting sexual conjugation and related processes in Saccharomyces cerevisiae. II. Genetic analysis of nonmating mutants. Genetics 76:273–288
Madhani HD, Fink GR (1997) Combinatorial control required for the specificity of yeast MAPK signaling. Science 275:1314–1317
Maleri S, Ge Q, Hackett EA, Wang Y, Dohlman HG, Errede B (2004) Persistent activation by constitutive Ste7 promotes Kss1-mediated invasive growth but fails to support Fus3-dependent mating in yeast. Mol Cell Biol 24:9221–9238
Marcus S, Polverino A, Barr M, Wigler M (1994) Complexes between STE5 and components of the pheromone-responsive mitogen-activated protein kinase module. Proc Natl Acad Sci USA 91:7762–7766
McClean MN, Mody A, Broach JR, Ramanathan S (2007) Cross-talk and decision making in MAP kinase pathways. Nat Genet 39:409–414
Miller JH (1972) Experiments in molecular genetics. Cold Spring Harbor Laboratory, Cold Spring Harbor
Mosch HU, Roberts RL, Fink GR (1996) Ras2 signals via the Cdc42/Ste20/mitogen-activated protein kinase module to induce filamentous growth in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 93:5352–5356
Mosch HU, Kubler E, Krappmann S, Fink GR, Braus GH (1999) Crosstalk between the Ras2p-controlled mitogen-activated protein kinase and cAMP pathways during invasive growth of Saccharomyces cerevisiae. Mol Biol Cell 10:1325–1335
Nakafuku M, Itoh H, Nakamura S, Kaziro Y (1987) Occurrence in Saccharomyces cerevisiae of a gene homologous to the cDNA coding for the alpha subunit of mammalian G proteins. Proc Natl Acad Sci USA 84:2140–2144
Palecek SP, Parikh AS, Kron SJ (2002) Sensing, signalling and integrating physical processes during Saccharomyces cerevisiae invasive and filamentous growth. Microbiology 148:893–907
Pan X, Heitman J (2000) Sok2 regulates yeast pseudohyphal differentiation via a transcription factor cascade that regulates cell–cell adhesion. Mol Cell Biol 20:8364–8372
Peter M, Neiman AM, Park HO, van Lohuizen M, Herskowitz I (1996) Functional analysis of the interaction between the small GTP binding protein Cdc42 and the Ste20 protein kinase in yeast. EMBO J 15:7046–7059
Pryciak PM, Huntress FA (1998) Membrane recruitment of the kinase cascade scaffold protein Ste5 by the Gβγ complex underlies activation of the yeast pheromone response pathway. Genes Dev 12:2684–2697
Reed SI, Hadwiger JA, Lorincz AT (1985) Protein kinase activity associated with the product of the yeast cell division cycle gene CDC28. Proc Natl Acad Sci USA 82:4055–4059
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
Roberts RL, Mosch HU, Fink GR (1997) 14–3-3 proteins are essential for RAS/MAPK cascade signaling during pseudohyphal development in S. cerevisiae. Cell 89:1055–1065
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
Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory manual. Cold Spring Harbor Laboratory, Cold Spring Harbor
Schaeffer HJ, Weber MJ (1999) Mitogen-activated protein kinases: specific messages from ubiquitous messengers. Mol Cell Biol 19:2435–2444
Schwartz MA, Madhani HD (2004) Principles of MAP kinase signaling specificity in Saccharomyces cerevisiae. Annu Rev Genet 38:725–748
Spiegel AM (1987) Signal transduction by guanine nucleotide binding proteins. Mol Cell Endocrinol 49:1–16
Spiegel A et al (1988) Signal transduction by guanine nucleotide-binding proteins. Recent Prog Horm Res 44:337–375
Stevenson BJ, Rhodes N, Errede B, Sprague GF Jr (1992) Constitutive mutants of the protein kinase STE11 activate the yeast pheromone response pathway in the absence of the G protein. Genes Dev 6:1293–1304
Stratton HF, Zhou J, Reed SI, Stone DE (1996) The mating-specific Gα protein of Saccharomyces cerevisiae downregulates the mating signal by a mechanism that is dependent on pheromone and independent of Gβγ sequestration. Mol Cell Biol 16:6325–6337
Trueheart J, Boeke JD, Fink GR (1987) Two genes required for cell fusion during yeast conjugation: evidence for a pheromone-induced surface protein. Mol Cell Biol 7:2316–2328
Whiteway M et al (1989) The STE4 and STE18 genes of yeast encode potential beta and gamma subunits of the mating factor receptor-coupled G protein. Cell 56:467–477
Whiteway M, Hougan L, Thomas DY (1990) Overexpression of the STE4 gene leads to mating response in haploid Saccharomyces cerevisiae. Mol Cell Biol 10:217–222
Whitmarsh AJ, Davis RJ (1998) Structural organization of MAP-kinase signaling modules by scaffold proteins in yeast and mammals. Trends Biochem Sci 23:481–485
Yashar B et al (1995) Yeast MEK-dependent signal transduction: response thresholds and parameters affecting fidelity. Mol Cell Biol 15:6545–6553
Acknowledgments
The authors would like to thank William Lu for technical assistance, and Beverly Errede and Peter Pryciak for strains and plasmids. This work was supported by National Science Foundation grant #MCB-0453964.
Author information
Authors and Affiliations
Corresponding author
Additional information
Communicated by S. Hohmann.
E. Draper and O. Dubrovskyi contributed equally to this work.
Rights and permissions
About this article
Cite this article
Draper, E., Dubrovskyi, O., Bar, E.E. et al. Dse1 may control cross talk between the pheromone and filamentation pathways in yeast. Curr Genet 55, 611–621 (2009). https://doi.org/10.1007/s00294-009-0274-6
Received:
Revised:
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s00294-009-0274-6