Synthetic biology: Lessons from engineering yeast MAPK signalling pathways

Molecular Microbiology

Volumn 88, Issue 1, 2013, Pages 5-19

  Furukawa, Kentaro ^a   Hohmann, Stefan ^a  

^a UNIVERSITY OF GOTHENBURG   (Sweden)

Author keywords

[No Author keywords available]

Indexed keywords

FUNGAL PROTEIN; MITOGEN ACTIVATED PROTEIN KINASE; MITOGEN ACTIVATED PROTEIN KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE KINASE 1; MITOGEN ACTIVATED PROTEIN KINASE PHOSPHATASE; PROTEIN MSG 5; PROTEIN PTP 2; PROTEIN PTP 3; PROTEIN SKN7; PROTEIN SLN1; PROTEIN YPD1; UNCLASSIFIED DRUG;

ANALYTICAL PARAMETERS; BIOTECHNOLOGY; CELL ENGINEERING; ENZYME ACTIVITY; ENZYME SPECIFICITY; HUMAN; MAMMAL CELL; MOLECULAR BIOLOGY; MOLECULAR EVOLUTION; NONHUMAN; PRIORITY JOURNAL; PROTEIN ENGINEERING; PROTEIN EXPRESSION; PROTEIN FUNCTION; PROTEIN LOCALIZATION; PROTEIN PHOSPHORYLATION; PROTEIN SYNTHESIS; REVIEW; SIGNAL TRANSDUCTION; SYNTHETIC BIOLOGY; YEAST;

GENETIC ENGINEERING; MAP KINASE SIGNALING SYSTEM; SACCHAROMYCES CEREVISIAE; SYNTHETIC BIOLOGY;

MAMMALIA; SACCHAROMYCES CEREVISIAE; SACCHAROMYCETALES;

EID: 84875622740     PISSN: 0950382X     EISSN: 13652958     Source Type: Journal    
DOI: 10.1111/mmi.12174     Document Type: Review

References (138)

1. Andrianantoandro, E., Basu, S., Karig, D.K., and Weiss, R. (2006) Synthetic biology: new engineering rules for an emerging discipline. Mol Syst Biol 2: 2006.0028.
2. Babiskin, A.H., and Smolke, C.D. (2011) A synthetic library of RNA control modules for predictable tuning of gene expression in yeast. Mol Syst Biol 7: 471.
3. Bao, M.Z., Schwartz, M.A., Cantin, G.T., Yates, J.R., 3rd, and Madhani, H.D. (2004) Pheromone-dependent destruction of the Tec1 transcription factor is required for MAP kinase signaling specificity in yeast. Cell 119: 991-1000.
4. Baranski, T.J., Herzmark, P., Lichtarge, O., Gerber, B.O., Trueheart, J., Meng, E.C., etal. (1999) C5a receptor activation. Genetic identification of critical residues in four transmembrane helices. J Biol Chem 274: 15757-15765.
5. Bardwell, L. (2005) A walk-through of the yeast mating pheromone response pathway. Peptides 26: 339-350.
6. Bashor, C.J., Helman, N.C., Yan, S., and Lim, W.A. (2008) Using engineered scaffold interactions to reshape MAP kinase pathway signaling dynamics. Science 319: 1539-1543.
7. Bashor, C.J., Horwitz, A.A., Peisajovich, S.G., and Lim, W.A. (2010) Rewiring cells: synthetic biology as a tool to interrogate the organizational principles of living systems. Annu Rev Biophys 39: 515-537.
8. Becskei, A., Seraphin, B., and Serrano, L. (2001) Positive feedback in eukaryotic gene networks: cell differentiation by graded to binary response conversion. EMBO J 20: 2528-2535.
9. Bellí, G., Garí, E., Piedrafita, L., Aldea, M., and Herrero, E. (1998) An activator/repressor dual system allows tight tetracycline-regulated gene expression in budding yeast. Nucleic Acids Res 26: 942-947.
10. Bilsland-Marchesan, E., Ariño, J., Saito, H., Sunnerhagen, P., and Posas, F. (2000) Rck2 kinase is a substrate for the osmotic stress-activated mitogen-activated protein kinase Hog1. Mol Cell Biol 20: 3887-3895.
11. Blazeck, J., Garg, R., Reed, B., and Alper, H.S. (2012) Controlling promoter strength and regulation in Saccharomyces cerevisiae using synthetic hybrid promoters. Biotechnol Bioeng 109: 2884-2895.
12. Blount, B.A., Weenink, T., and Ellis, T. (2012a) Construction of synthetic regulatory networks in yeast. FEBS Lett 586: 2112-2121.
13. Blount, B.A., Weenink, T., Vasylechko, S., and Ellis, T. (2012b) Rational diversification of a promoter providing fine-tuned expression and orthogonal regulation for synthetic biology. PLoS ONE 7: e33279.
14. Botstein, D., and Fink, G.R. (2011) Yeast: an experimental organism for 21st century biology. Genetics 189: 695-704.
15. Bouwman, J., Kiewiet, J., Lindenbergh, A., van Eunen, K., Siderius, M., and Bakker, B.M. (2011) Metabolic regulation rather than de novo enzyme synthesis dominates the osmo-adaptation of yeast. Yeast 28: 43-53.
16. Brenner, K., You, L., and Arnold, F.H. (2008) Engineering microbial consortia: a new frontier in synthetic biology. Trends Biotechnol 26: 483-489.
17. Brent, R. (2009) Cell signaling: what is the signal and what information does it carry? FEBS Lett 583: 4019-4024.
18. Broach, J.R., and Thorner, J. (1996) High-throughput screening for drug discovery. Nature 384: 14-16.
19. Canton, B., Labno, A., and Endy, D. (2008) Refinement and standardization of synthetic biological parts and devices. Nat Biotechnol 26: 787-793.
20. Chen, M.T., and Weiss, R. (2005) Artificial cell-cell communication in yeast Saccharomyces cerevisiae using signaling elements from Arabidopsis thaliana. Nat Biotechnol 23: 1551-1555.
21. Chen, R.E., and Thorner, J. (2007) Function and regulation in MAPK signaling pathways: lessons learned from the yeast Saccharomyces cerevisiae. Biochim Biophys Acta 1773: 1311-1340.
22. Chen, R.E., Patterson, J.C., Goupil, L.S., and Thorner, J. (2010) Dynamic localization of Fus3 mitogen-activated protein kinase is necessary to evoke appropriate responses and avoid cytotoxic effects. Mol Cell Biol 30: 4293-4307.
23. Cheng, A.A., and Lu, T.K. (2012) Synthetic biology: an emerging engineering discipline. Annu Rev Biomed Eng 14: 155-178.
24. Cdc4 determines MAPK signaling specificity during mating in yeast. Cell 119: 981-990.
25. Cullen, P.J., and Sprague, G.F., Jr. (2012) The regulation of filamentous growth in yeast. Genetics 190: 23-49.
26. Dohmen, R.J., Wu, P., and Varshavsky, A. (1994) Heat-inducible degron: a method for constructing temperature-sensitive mutants. Science 263: 1273-1276.
27. van Drogen, F., Stucke, V.M., Jorritsma, G., and Peter, M. (2001) MAP kinase dynamics in response to pheromones in budding yeast. Nat Cell Biol 3: 1051-1059.
28. Dymond, J.S., Richardson, S.M., Coombes, C.E., Babatz, T., Muller, H., Annaluru, N., etal. (2011) Synthetic chromosome arms function in yeast and generate phenotypic diversity by design. Nature 477: 471-476.
29. Elowitz, M.B., and Leibler, S. (2000) A synthetic oscillatory network of transcriptional regulators. Nature 403: 335-338.
30. Erlenbach, I., Kostenis, E., Schmidt, C., Serradeil-Le Gal, C., Raufaste, D., Dumont, M.E., etal. (2001) Single amino acid substitutions and deletions that alter the G protein coupling properties of the V2 vasopressin receptor identified in yeast by receptor random mutagenesis. J Biol Chem 276: 29382-29392.
31. Esch, R.K., and Errede, B. (2002) Pheromone induction promotes Ste11 degradation through a MAPK feedback and ubiquitin-dependent mechanism. Proc Natl Acad Sci USA 99: 9160-9165.
32. Fassler, J.S., Gray, W.M., Malone, C.L., Tao, W., Lin, H., and Deschenes, R.J. (1997) Activated alleles of yeast SLN1 increase Mcm1-dependent reporter gene expression and diminish signaling through the Hog1 osmosensing pathway. J Biol Chem 272: 13365-13371.
33. Ferrell, J.E., Jr. (2002) Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability. Curr Opin Cell Biol 14: 140-148.
34. Ferrigno, P., Posas, F., Koepp, D., Saito, H., and Silver, P.A. (1998) Regulated nucleo/cytoplasmic exchange of HOG1 MAPK requires the importin β homologs NMD5 and XPO1. EMBO J 17: 5606-5614.
35. Furukawa, K., Sidoux-Walter, F., and Hohmann, S. (2009) Expression of the yeast aquaporin Aqy2 affects cell surface properties under the control of osmoregulatory and morphogenic signalling pathways. Mol Microbiol 74: 1272-1286.
36. Furukawa, K., Randhawa, A., Kaur, H., Mondal, A.K., and Hohmann, S. (2012) Fungal fludioxonil sensitivity is diminished by a constitutively active form of the group III histidine kinase. FEBS Lett 586: 2417-2422.
37. Gardner, T.S., Cantor, C.R., and Collins, J.J. (2000) Construction of a genetic toggle switch in Eschicheria coli. Nature 403: 339-342.
38. Garí, E., Piedrafita, L., Aldea, M., and Herrero, E. (1997) A set of vectors with a tetracycline-regulatable promoter system for modulated gene expression in Saccharomyces cerevisiae. Yeast 13: 837-848.
39. Giaever, G., Chu, A.M., Ni, L., Connelly, C., Riles, L., Véronneau, S., etal. (2002) Functional profiling of the Saccharomyces cerevisiae genome. Nature 418: 387-391.
40. Gustin, M.C., Albertyn, J., Alexander, M., and Davenport, K. (1998) MAP kinase pathways in the yeast Saccharomyces cerevisiae. Microbiol Mol Biol Rev 62: 1264-1300.
41. Hagen, D.C., McCaffrey, G., and Sprague, G.F., Jr. (1991) Pheromone response elements are necessary and sufficient for basal and pheromone-induced transcription of the FUS1 gene of Saccharomyces cerevisiae. Mol Cell Biol 11: 2952-2961.
42. Haruki, H., Nishikawa, J., and Laemmli, U.K. (2008) The anchor-away technique: rapid, conditional establishment of yeast mutant phenotypes. Mol Cell 31: 925-932.
43. Hersen, P., McClean, M.N., Mahadevan, L., and Ramanathan, S. (2008) Signal processing by the HOG MAP kinase pathway. Proc Natl Acad Sci USA 105: 7165-7170.
44. Hohmann, S. (2002) Osmotic stress signaling and osmoadaptation in yeasts. Microbiol Mol Biol Rev 66: 300-372.
45. Hohmann, S. (2009) Control of high osmolarity signalling in the yeast Saccharomyces cerevisiae. FEBS Lett 583: 4025-4029.
46. Huh, W.K., Falvo, J.V., Gerke, L.C., Carroll, A.S., Howson, R.W., Weissman, J.S., and O'Shea, E.K. (2003) Global analysis of protein localization in budding yeast. Nature 425: 686-691.
47. Ingolia, N.T., and Murray, A.W. (2007) Positive-feedback loops as a flexible biological module. Curr Biol 17: 668-677.
48. Inoue, T., Higuchi, M., Hashimoto, Y., Seki, M., Kobayashi, M., Kato, T., etal. (2001) Identification of CRE1 as a cytokinin receptor from Arabidopsis. Nature 409: 1060-1063.
49. Johnston, M., and Davis, R.W. (1984) Sequences that regulate the divergent GAL1-GAL10 promoter in Saccharomyces cerevisiae. Mol Cell Biol 4: 1440-1448.
50. Jungbluth, M., Renicke, C., and Taxis, C. (2010) Targeted protein depletion in Saccharomyces cerevisiae by activation of a bidirectional degron. BMC Syst Biol 4: 176.
51. Keasling, J.D. (2010) Manufacturing molecules through metabolic engineering. Science 330: 1355-1358.
52. Khalil, A.S., and Collins, J.J. (2010) Synthetic biology: applications come of age. Nat Rev Genet 11: 367-379.
53. Khalil, A.S., Lu, T.K., Bashor, C.J., Ramirez, C.L., Pyenson, N.C., Joung, J.K., and Collins, J.J. (2012) A synthetic biology framework for programming eukaryotic transcription functions. Cell 150: 647-658.
54. Kholodenko, B.N. (2006) Cell-signalling dynamics in time and space. Nat Rev Mol Cell Biol 7: 165-176.
55. Kiel, C., Yus, E., and Serrano, L. (2010) Engineering signal transduction pathways. Cell 140: 33-47.
56. King, K., Dohlman, H.G., Thorner, J., Caron, M.G., and Lefkowitz, R.J. (1990) Control of yeast mating signal transduction by a mammalian beta 2-adrenergic receptor and Gs alpha subunit. Science 250: 121-123.
57. Kitano, H. (2004) Biological robustness. Nat Rev Genet 5: 826-837.
58. Klein, C., Paul, J.I., Sauvé, K., Schmidt, M.M., Arcangeli, L., Ransom, J., etal. (1998) Identification of surrogate agonists for the human FPRL-1 receptor by autocrine selection in yeast. Nat Biotechnol 16: 1334-1337.
59. Klein, M., Morillas, M., Vendrell, A., Brive, L., Gebbia, M., Wallace, I.M., etal. (2011) Design, synthesis and characterization of a highly effective inhibitor for analog-sensitive (as) kinases. PLoS ONE 6: e20789.
60. Klipp, E. (2011) Computational yeast systems biology: a case study for the MAP kinase cascade. Methods Mol Biol 759: 323-343.
61. Klipp, E., Nordlander, B., Krüger, R., Gennemark, P., and Hohmann, S. (2005) Integrative model of the response of yeast to osmotic shock. Nat Biotechnol 23: 975-982.
62. Krantz, M., Ahmadpour, D., Ottosson, L.G., Warringer, J., Waltermann, C., Nordlander, B., etal. (2009) Robustness and fragility in the yeast high osmolarity glycerol (HOG) signal-transduction pathway. Mol Syst Biol 5: 281.
63. Kwok, R. (2010) Five hard truths for synthetic biology. Nature 463: 288-290.
64. Lengeler, K.B., Davidson, R.C., D'souza, C., Harashima, T., Shen, W.C., Wang, P., etal. (2000) Signal transduction cascades regulating fungal development and virulence. Microbiol Mol Biol Rev 64: 746-785.
65. Levin, D.E. (2005) Cell wall integrity signaling in Saccharomyces cerevisiae. Microbiol Mol Biol Rev 69: 262-291.
66. Levin, D.E. (2011) Regulation of cell wall biogenesis in Saccharomyces cerevisiae: the cell wall integrity signaling pathway. Genetics 189: 1145-1175.
67. Li, S., Ault, A., Malone, C.L., Raitt, D., Dean, S., Johnston, L.H., etal. (1998) The yeast histidine protein kinase, Sln1p, mediates phosphotransfer to two response regulators, Ssk1p and Skn7p. EMBO J 17: 6952-6962.
68. Li, Z., Vizeacoumar, F.J., Bahr, S., Li, J., Warringer, J., Vizeacoumar, F.S., etal. (2011) Systematic exploration of essential yeast gene function with temperature-sensitive mutants. Nat Biotechnol 29: 361-367.
69. Lim, W.A. (2010) Designing customized cell signalling circuits. Nat Rev Mol Cell Biol 11: 393-403.
70. Louvion, J.F., Havaux-Copf, B., and Picard, D. (1993) Fusion of GAL4-VP16 to a steroid-binding domain provides a tool for gratuitous induction of galactose-responsive genes in yeast. Gene 131: 129-134.
71. Lu, J.M., Deschenes, R.J., and Fassler, J.S. (2003) Saccharomyces cerevisiae histidine phosphotransferase Ypd1p shuttles between the nucleus and cytoplasm for SLN1-dependent phosphorylation of Ssk1p and Skn7p. Eukaryot Cell 2: 1304-1314.
72. Lu, T.K., Khalil, A.S., and Collins, J.J. (2009) Next-generation synthetic gene networks. Nat Biotechnol 27: 1139-1150.
73. McClean, M.N., Mody, A., Broach, J.R., and Ramanathan, S. (2007) Cross-talk and decision making in MAP kinase pathways. Nat Genet 39: 409-414.
74. Macía, J., Regot, S., Peeters, T., Conde, N., Solé, R., and Posas, F. (2009) Dynamic signaling in the Hog1 MAPK pathway relies on high basal signal transduction. Sci Signal 2: ra13.
75. McIsaac, R.S., Silverman, S.J., McClean, M.N., Gibney, P.A., Macinskas, J., Hickman, M.J., etal. (2011) Fast-acting and nearly gratuitous induction of gene expression and protein depletion in Saccharomyces cerevisiae. Mol Biol Cell 22: 4447-4459.
76. Maeda, T., Wurgler-Murphy, S.M., and Saito, H. (1994) A two-component system that regulates an osmosensing MAP kinase cascade in yeast. Nature 369: 242-245.
77. Maeda, T., Takekawa, M., and Saito, H. (1995) Activation of yeast PBS2 MAPKK by MAPKKKs or by binding of an SH3-containing osmosensor. Science 269: 554-558.
78. Meena, N., Kaur, H., and Mondal, A.K. (2010) Interactions among HAMP domain repeats act as an osmosensing molecular switch in group III hybrid histidine kinases from fungi. J Biol Chem 285: 12121-12132.
79. Mettetal, J.T., Muzzey, D., Gómez-Uribe, C., and van Oudenaarden, A. (2008) The frequency dependence of osmo-adaptation in Saccharomyces cerevisiae. Science 319: 482-484.
80. Minic, J., Persuy, M.A., Godel, E., Aioun, J., Connerton, I., Salesse, R., and Pajot-Augy, E. (2005) Functional expression of olfactory receptors in yeast and development of a bioassay for odorant screening. FEBS J 272: 524-537.
81. Mody, A., Weiner, J., and Ramanathan, S. (2009) Modularity of MAP kinases allows deformation of their signalling pathways. Nat Cell Biol 11: 484-491.
82. Moriya, H., Shimizu-Yoshida, Y., and Kitano, H. (2006) In vivo robustness analysis of cell division cycle genes in Saccharomyces cerevisiae. PLoS Genet 2: e111.
83. Muzzey, D., Gómez-Uribe, C.A., Mettetal, J.T., and van Oudenaarden, A. (2009) A systems-level analysis of perfect adaptation in yeast osmoregulation. Cell 138: 160-171.
84. de Nadal, E., Casadomé, L., and Posas, F. (2003) Targeting the MEF2-like transcription factor Smp1 by the stress-activated Hog1 mitogen-activated protein kinase. Mol Cell Biol 23: 229-237.
85. Nandagopal, N., and Elowitz, M.B. (2011) Synthetic biology: integrated gene circuits. Science 333: 1244-1248.
86. Nishimura, K., Fukagawa, T., Takisawa, H., Kakimoto, T., and Kanemaki, M. (2009) An auxin-based degron system for the rapid depletion of proteins in nonplant cells. Nat Methods 6: 917-922.
87. O'Rourke, S.M., and Herskowitz, I. (1998) The Hog1 MAPK prevents cross talk between the HOG and pheromone response MAPK pathways in Saccharomyces cerevisiae. Genes Dev 12: 2874-2886.
88. O'Shaughnessy, E.C., and Sarkar, C.A. (2012) Analyzing and engineering cell signaling modules with synthetic biology. Curr Opin Biotechnol 23: 785-790.
89. O'Shaughnessy, E.C., Palani, S., Collins, J.J., and Sarkar, C.A. (2011) Tunable signal processing in synthetic MAP kinase cascades. Cell 144: 119-131.
90. Özcan, S., and Johnston, M. (1995) Three different regulatory mechanisms enable yeast hexose transporter (HXT) genes to be induced by different levels of glucose. Mol Cell Biol 15: 1564-1572.
91. Park, S.H., Zarrinpar, A., and Lim, W.A. (2003) Rewiring MAP kinase pathways using alternative scaffold assembly mechanisms. Science 299: 1061-1064.
92. Partow, S., Siewers, V., Bjørn, S., Nielsen, J., and Maury, J. (2010) Characterization of different promoters for designing a new expression vector in Saccharomyces cerevisiae. Yeast 27: 955-964.
93. Patterson, J.C., Klimenko, E.S., and Thorner, J. (2010) Single-cell analysis reveals that insulation maintains signaling specificity between two yeast MAPK pathways with common components. Sci Signal 3: ra75.
94. Patwardhan, P., and Miller, W.T. (2007) Processive phosphorylation: mechanism and biological importance. Cell Signal 19: 2218-2226.
95. Pausch, M.H. (1997) G-protein-coupled receptors in Saccharomyces cerevisiae: high-throughput screening assays for drug discovery. Trends Biotechnol 15: 487-494.
96. Peisajovich, S.G., Garbarino, J.E., Wei, P., and Lim, W.A. (2010) Rapid diversification of cell signaling phenotypes by modular domain recombination. Science 328: 368-372.
97. Pelet, S., Rudolf, F., Nadal-Ribelles, M., de Nadal, E., Posas, F., and Peter, M. (2011) Transient activation of the HOG MAPK pathway regulates bimodal gene expression. Science 332: 732-735.
98. Posas, F., and Saito, H. (1998) Activation of the yeast SSK2 MAP kinase kinase kinase by the SSK1 two-component response regulator. EMBO J 17: 1385-1394.
99. Price, L.A., Kajkowski, E.M., Hadcock, J.R., Ozenberger, B.A., and Pausch, M.H. (1995) Functional coupling of a mammalian somatostatin receptor to the yeast pheromone response pathway. Mol Cell Biol 15: 6188-6195.
100. Pryciak, P.M. (2009) Designing new cellular signaling pathways. Chem Biol 16: 249-254.
101. Purnick, P.E., and Weiss, R. (2009) The second wave of synthetic biology: from modules to systems. Nat Rev Mol Cell Biol 10: 410-422.
102. Regot, S., Macía, J., Conde, N., Furukawa, K., Kjellén, J., Peeters, T., etal. (2011) Distributed biological computation with multicellular engineered networks. Nature 469: 207-211.
103. Ribet, D., and Cossart, P. (2010) Pathogen-mediated posttranslational modifications: a re-emerging field. Cell 143: 694-702.
104. Ro, D.K., Paradise, E.M., Ouellet, M., Fisher, K.J., Newman, K.L., Ndungu, J.M., etal. (2006) Production of the antimalarial drug precursor artemisinic acid in engineered yeast. Nature 440: 940-943.
105. Ruder, W.C., Lu, T., and Collins, J.J. (2011) Synthetic biology moving into the clinic. Science 333: 1248-1252.
106. Saito, H. (2010) Regulation of cross-talk in yeast MAPK signaling pathways. Curr Opin Microbiol 13: 677-683.
107. Saito, H., and Posas, F. (2012) Response to hyperosmotic stress. Genetics 192: 289-318.
108. Salomon, D., Bosis, E., Dar, D., Nachman, I., and Sessa, G. (2012) Expression of Pseudomonas syringae type III effectors in yeast under stress conditions reveals that HopX1 attenuates activation of the high osmolarity glycerol MAP kinase pathway. Microbiology 158: 2859-2869.
109. Sato, N., Kawahara, H., Toh-e, A., and Maeda, T. (2003) Phosphorelay-regulated degradation of the yeast Ssk1p response regulator by the ubiquitin-proteasome system. Mol Cell Biol 23: 6662-6671.
110. Schaber, J., Adrover, M.A., Eriksson, E., Pelet, S., Petelenz-Kurdziel, E., Klein, D., etal. (2010) Biophysical properties of Saccharomyces cerevisiae and their relationship with HOG pathway activation. Eur Biophys J 39: 1547-1556.
111. Schwartz, M.A., and Madhani, H.D. (2004) Principles of MAP kinase signaling specificity in Saccharomyces cerevisiae. Annu Rev Genet 38: 725-748.
112. Shaner, N.C., Steinbach, P.A., and Tsien, R.Y. (2005) A guide to choosing fluorescent proteins. Nat Methods 2: 905-909.
113. Sharon, E., Kalma, Y., Sharp, A., Raveh-Sadka, T., Levo, M., Zeevi, D., etal. (2012) Inferring gene regulatory logic from high-throughput measurements of thousands of systematically designed promoters. Nat Biotechnol 30: 521-530.
114. Slusarczyk, A.L., Lin, A., and Weiss, R. (2012) Foundations for the design and implementation of synthetic genetic circuits. Nat Rev Genet 13: 406-420.
115. Smolke, C.D. (2009) Building outside of the box: iGEM and the BioBricks Foundation. Nat Biotechnol 27: 1099-1102.
116. Smolke, C.D., and Silver, P.A. (2011) Informing biological design by integration of systems and synthetic biology. Cell 144: 855-859.
117. Steen, E.J., Chan, R., Prasad, N., Myers, S., Petzold, C.J., Redding, A., etal. (2008) Metabolic engineering of Saccharomyces cerevisiae for the production of n-butanol. Microb Cell Fact 7: 36.
118. Stevenson, B.J., Rhodes, N., Errede, B., and Sprague, G.F., 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.
119. Strickland, D., Lin, Y., Wagner, E., Hope, C.M., Zayner, J., Antoniou, C., etal. (2012) TULIPs: tunable, light-controlled interacting protein tags for cell biology. Nat Methods 9: 379-384.
120. Sun, J., Shao, Z., Zhao, H., Nair, N., Wen, F., Xu, J.H., and Zhao, H. (2012) Cloning and characterization of a panel of constitutive promoters for applications in pathway engineering in Saccharomyces cerevisiae. Biotechnol Bioeng 109: 2082-2092.
121. Takahashi, S., and Pryciak, P.M. (2008) Membrane localization of scaffold proteins promotes graded signaling in the yeast MAP kinase cascade. Curr Biol 18: 1184-1191.
122. Tanaka, H., and Yi, T.M. (2009) Synthetic morphology using alternative inputs. PLoS ONE 4: e6946.
123. Tatebayashi, K., Takekawa, M., and Saito, H. (2003) A docking site determining specificity of Pbs2 MAPKK for Ssk2/Ssk22 MAPKKKs in the yeast HOG pathway. EMBO J 22: 3624-3634.
124. Tatebayashi, K., Yamamoto, K., Tanaka, K., Tomida, T., Maruoka, T., Kasukawa, E., and Saito, H. (2006) Adaptor functions of Cdc42, Ste50, and Sho1 in the yeast osmoregulatory HOG MAPK pathway. EMBO J 25: 3033-3044.
125. Tatebayashi, K., Tanaka, K., Yang, H.Y., Yamamoto, K., Matsushita, Y., Tomida, T., etal. (2007) Transmembrane mucins Hkr1 and Msb2 are putative osmosensors in the SHO1 branch of yeast HOG pathway. EMBO J 26: 3521-3533.
126. Taxis, C., Stier, G., Spadaccini, R., and Knop, M. (2009) Efficient protein depletion by genetically controlled deprotection of a dormant N-degron. Mol Syst Biol 5: 267.
127. Tebbets, B., Stewart, D., Lawry, S., Nett, J., Nantel, A., Andes, D., and Klein, B.S. (2012) Identification and characterization of antifungal compounds using a Saccharomyces cerevisiae reporter bioassay. PLoS ONE 7: e36021.
128. Thorsen, M., Di, Y., Tängemo, C., Morillas, M., Ahmadpour, D., Van der Does, C., etal. (2006) The MAPK Hog1p modulates Fps1p-dependent arsenite uptake and tolerance in yeast. Mol Biol Cell 17: 4400-4410.
129. Tiger, C.F., Krause, F., Cedersund, G., Palmér, R., Klipp, E., Hohmann, S., etal. (2012) A framework for mapping, visualisation and automatic model creation of signal-transduction networks. Mol Syst Biol 8: 578.
130. Wei, P., Wong, W.W., Park, J.S., Corcoran, E.E., Peisajovich, S.G., Onuffer, J.J., etal. (2012) Bacterial virulence proteins as tools to rewire kinase pathways in yeast and immune cells. Nature 488: 384-388.
131. Westfall, P.J., and Thorner, J. (2006) Analysis of mitogen-activated protein kinase signaling specificity in response to hyperosmotic stress: use of an analog-sensitive HOG1 allele. Eukaryot Cell 5: 1215-1228.
132. Westfall, P.J., Patterson, J.C., Chen, R.E., and Thorner, J. (2008) Stress resistance and signal fidelity independent of nuclear MAPK function. Proc Natl Acad Sci USA 105: 12212-12217.
133. Widmann, C., Gibson, S., Jarpe, M.B., and Johnson, G.L. (1999) Mitogen-activated protein kinase: conservation of a three-kinase module from yeast to human. Physiol Rev 79: 143-180.
134. Winters, M.J., Lamson, R.E., Nakanishi, H., Neiman, A.M., and Pryciak, P.M. (2005) A membrane binding domain in the Ste5 scaffold synergizes with Gβγ binding to control localization and signaling in pheromone response. Mol Cell 20: 21-32.
135. Won, A.P., Garbarino, J.E., and Lim, W.A. (2011) Recruitment interactions can override catalytic interactions in determining the functional identity of a protein kinase. Proc Natl Acad Sci USA 108: 9809-9814.
136. Yang, H.Y., Tatebayashi, K., Yamamoto, K., and Saito, H. (2009) Glycosylation defects activate filamentous growth Kss1 MAPK and inhibit osmoregulatory Hog1 MAPK. EMBO J 28: 1380-1391.
137. Yoshimi, A., Kojima, K., Takano, Y., and Tanaka, C. (2005) Group III histidine kinase is a positive regulator of Hog1-type mitogen-activated protein kinase in filamentous fungi. Eukaryot Cell 4: 1820-1828.
138. Zarrinpar, A., Park, S.H., and Lim, W.A. (2003) Optimization of specificity in a cellular protein interaction network by negative selection. Nature 426: 676-680.