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Modelling signalling pathways – a yeast approach

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Systems Biology

Part of the book series: Topics in Current Genetics ((TCG,volume 13))

Abstract

MAP kinase pathways are conserved signalling systems in eukaryotes that control stress responses, cell growth, and proliferation, as well as differentiation. Here, we discuss and compare the feedback control mechanisms of two very well studied yeast signalling systems: the pheromone response pathway and the osmosensing HOG pathway. Mathematical models have recently been generated, allowing in silico analysis of signalling properties of both pathways. To advance our understanding of pathway control and to make modelling less dependent on parameter estimation, quantitative time course data of high precision and resolution need to be generated in the future and implemented into mathematical models. We expect that a combination of quantitative analyses and modelling/simulation will provide novel insight into the rules with which signalling pathways control cellular processes.

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References

  • 1. Alepuz PM, de Nadal E, Zapater M, Ammerer G, Posas F (2003) Osmostress-induced transcription by Hot1 depends on a Hog1-mediated recruitment of the RNA Pol II. EMBO J 22:2433-2442

    Article  PubMed  Google Scholar 

  • 2. Alepuz PM, Jovanovic A, Reiser V, Ammerer G (2001) Stress-induced MAP kinase Hog1 is part of transcription activation complexes. Mol Cell 7:767-777

    Article  PubMed  Google Scholar 

  • 3. Asthagiri AR, Lauffenburger DA (2000) Bioengineering models of cell signaling. Annu Rev Biomed Eng 2:31-53

    Article  PubMed  Google Scholar 

  • 4. Bardwell L (2004) A walk-through of the yeast mating pheromone response pathway. Peptides 25:1465-1476

    Article  PubMed  Google Scholar 

  • 5. Barkai N, Leibler S (1997) Robustness in simple biochemical networks. Nature 387:913-917

    Article  PubMed  Google Scholar 

  • 6. Bhalla US, Iyengar R (2001) Robustness of the bistable behavior of a biological signaling feedback loop. Chaos 11:221-226

    Article  PubMed  Google Scholar 

  • 7. Bluthgen N, Herzel H (2003) How robust are switches in intracellular signaling cascades? J Theor Biol 225:293-300

    Article  PubMed  Google Scholar 

  • 8. Brightman FA, Fell DA (2000) Differential feedback regulation of the MAPK cascade underlies the quantitative differences in EGF and NGF signalling in PC12 cells. FEBS Lett 482:169-174

    Article  PubMed  Google Scholar 

  • 9. Bustin SA (2002) Quantification of mRNA using real-time reverse transcription PCR (RT-PCR): trends and problems. J Mol Endocrinol 29:23-39

    Article  PubMed  Google Scholar 

  • 10. de Nadal E, Alepuz PM, Posas F (2002) Dealing with osmostress through MAP kinase activation. EMBO Rep 3:735-740

    Article  PubMed  Google Scholar 

  • 11. De Nadal E, Zapater M, Alepuz PM, Sumoy L, Mas G, Posas F (2004) The MAPK Hog1 recruits Rpd3 histone deacetylase to activate osmoresponsive genes. Nature 427:370-374

    Article  PubMed  Google Scholar 

  • 12. Dihazi H, Kessler R, Eschrich K (2004) HOG-pathway induced phosphorylation and activation of 6-phosphofructo-2-kinase are essential for glycerol accumulation and yeast cell proliferation under hyperosmotic stress. J Biol Chem 279:23961-23968

    Article  PubMed  Google Scholar 

  • 13. Dohlman HG, Thorner JW (2001) Regulation of G protein-initiated signal transduction in yeast: paradigms and principles. Annu Rev Biochem 70:703-754

    Article  PubMed  Google Scholar 

  • 14. Elion EA (2000) Pheromone response, mating and cell biology. Curr Opin Microbiol 3:573-581

    Article  PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • 16. Enger J, Goksör M, Ramser K, Hagberg P, Hanstorp D (2004) Optical tweezers applied to a microfluidic system. Lab Chip 4:196-200

    Article  PubMed  Google Scholar 

  • 17. Ericsson M, Hanstorp D, Hagberg P, Enger J, Nystrom T (2000) Sorting out bacterial viability with optical tweezers. J Bacteriol 182:5551-5555

    Article  PubMed  Google Scholar 

  • 18. Escote X, Zapater M, Clotet J, Posas F (2004) Hog1 mediates cell-cycle arrest in G1 phase by the dual targeting of Sic1. Nat Cell Biol 6:997-1002

    Article  PubMed  Google Scholar 

  • 19. Ferrell JE Jr (2002) Self-perpetuating states in signal transduction: positive feedback, double-negative feedback and bistability. Curr Opin Cell Biol 14:140-148

    Article  PubMed  Google Scholar 

  • 20. Ghaemmaghami S, Huh WK, Bower K, Howson RW, Belle A, Dephoure N, O'Shea EK, Weissman JS (2003) Global analysis of protein expression in yeast. Nature 425:737-741

    Article  PubMed  Google Scholar 

  • 21. Goldbeter A, Koshland DE Jr (1984) Ultrasensitivity in biochemical systems controlled by covalent modification. Interplay between zero-order and multistep effects. J Biol Chem 259:14441-14447

    PubMed  Google Scholar 

  • 22. Gordon GW, Berry G, Liang XH, Levine B, Herman B (1998) Quantitative fluorescence resonance energy transfer measurements using fluorescence microscopy. Biophys J 74:2702-2713

    PubMed  Google Scholar 

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

    PubMed  Google Scholar 

  • 24. Heinrich R, Neel BG, Rapoport TA (2002) Mathematical models of protein kinase signal transduction. Mol Cell 9:957-970

    Google Scholar 

  • 25. Herskowitz I (1995) MAP kinase pathways in yeast: for mating and more. Cell 80:187-197

    Article  PubMed  Google Scholar 

  • 26. Herskowitz I (1997) Building organs and organisms: elements of morphogenesis exhibited by budding yeast. Cold Spring Harb Symp Quant Biol 62:57-63

    PubMed  Google Scholar 

  • 27. Hohmann S (2002) Osmotic adaptation in yeast–control of the yeast osmolyte system. Int Rev Cytol 215:149-187

    PubMed  Google Scholar 

  • 28. Hohmann S (2002) Osmotic stress signaling and osmoadaptation in yeasts. Microbiol Mol Biol Rev 66:300-372

    Article  PubMed  Google Scholar 

  • 29. Huang CY, Ferrell JE Jr (1996) Ultrasensitivity in the mitogen-activated protein kinase cascade. Proc Natl Acad Sci USA 93:10078-10083

    Article  PubMed  Google Scholar 

  • 30. Kholodenko BN (2000) Negative feedback and ultrasensitivity can bring about oscillations in the mitogen-activated protein kinase cascades. Eur J Biochem 267:1583-1588

    Article  PubMed  Google Scholar 

  • 31. Klipp E, Nordlander B, Krüger R, Gennemark P, Hohmann S (2004) The dynamic response of yeast cells to osmotic shock - a systems biology approach. Nat Biotechnol under revision

    Google Scholar 

  • 32. Kofahl B, Klipp E (2004) Modelling the dynamics of the yeast pheromone pathway. Yeast 21:831-850

    Article  PubMed  Google Scholar 

  • 33. Krauss G (2001) Biochemistry of Signal Transduction and Regulation. Second Edition, Wiley-VCH, Weinheim ISBN 3-527-30378-2

    Google Scholar 

  • 34. Kusari AB, Molina DM, Sabbagh W Jr, Lau CS, Bardwell L (2004) A conserved protein interaction network involving the yeast MAP kinases Fus3 and Kss1. J Cell Biol 164:267-277

    Article  PubMed  Google Scholar 

  • 35. Lippincott-Schwartz J, Snapp E, Kenworthy A (2001) Studying protein dynamics in living cells. Nat Rev Mol Cell Biol 2:444-456

    Article  PubMed  Google Scholar 

  • 36. Llorens M, Nuno JC, Rodriguez Y, Melendez-Hevia E, Montero F (1999) Generalization of the theory of transition times in metabolic pathways: a geometrical approach. Biophys J 77:23-36

    PubMed  Google Scholar 

  • 37. MacBeath G (2002) Protein microarrays and proteomics. Nat Genet 32 Suppl:526-532

    Article  Google Scholar 

  • 38. Manney TR (1983) Expression of the BAR1 gene in Saccharomyces cerevisiae: induction by the alpha mating pheromone of an activity associated with a secreted protein. J Bacteriol 155:291-301

    PubMed  Google Scholar 

  • 39. Marsh L, Neiman AM, Herskowitz I (1991) Signal transduction during pheromone response in yeast. Annu Rev Cell Biol 7:699-728

    Article  PubMed  Google Scholar 

  • 40. Nielsen UB, Cardone MH, Sinskey AJ, MacBeath G, Sorger PK (2003) Profiling receptor tyrosine kinase activation by using Ab microarrays. Proc Natl Acad Sci USA 100:9330-9335

    Article  PubMed  Google Scholar 

  • 41. O'Rourke SM, Herskowitz I, O'Shea EK (2002) Yeast go the whole HOG for the hyperosmotic response. Trends Genet 18:405-412

    Article  PubMed  Google Scholar 

  • 42. Raitt DC, Posas F, Saito H (2000) Yeast Cdc42 GTPase and Ste20 PAK-like kinase regulate Sho1-dependent activation of the Hog1 MAPK pathway. EMBO J 19:4623-4631

    Article  PubMed  Google Scholar 

  • 43. Reiser V, Salah SM, Ammerer G (2000) Polarized localization of yeast Pbs2 depends on osmostress, the membrane protein Sho1 and Cdc42. Nat Cell Biol 2:620-627

    Article  PubMed  Google Scholar 

  • 44. Rieseberg M, Kasper C, Reardon KF, Scheper T (2001) Flow cytometry in biotechnology. Appl Microbiol Biotechnol 56:350-360

    Article  PubMed  Google Scholar 

  • 45. Sato N, Kawahara H, Toh-e A, Maeda T (2003) Phosphorelay-regulated degradation of the yeast Ssk1p response regulator by the ubiquitin-proteasome system. Mol Cell Biol 23:6662-6671

    Article  PubMed  Google Scholar 

  • 46. Seet BT, Pawson T (2004) MAPK signaling: Sho business. Curr Biol 14:R708-710

    Article  PubMed  Google Scholar 

  • 47. Specht KM, Shokat KM (2002) The emerging power of chemical genetics. Curr Opin Cell Biol 14:155-159

    Article  PubMed  Google Scholar 

  • 48. Sprague GF, Cullen PJ, Goehring AS (2004) Yeast signal transduction: regulation and interface with cell biology. Adv Exp Med Biol 547:91-105

    PubMed  Google Scholar 

  • 49. Sprague GFJ, Thorner JW (1992) Pheromone response and signal transduction during the mating process of Saccharomyces cerevisiae. In: Jones EW, Pringle JR, Broach JR (eds) The molecular and cellular biology of the yeast Saccharomyces. Gene expression. Cold Spring Harbor Laboratory Press, Cold Spring Harbor, pp 657-744

    Google Scholar 

  • 50. Swameye I, Muller TG, Timmer J, Sandra O, Klingmuller U (2003) Identification of nucleocytoplasmic cycling as a remote sensor in cellular signaling by databased modeling. Proc Natl Acad Sci USA 100:1028-1033

    Article  PubMed  Google Scholar 

  • 51. Támas MJ, Hohmann S (2003) The osmotic stress response of Saccharomyces cerevisiae. Topics Curr Genet 1:121-200

    Google Scholar 

  • 52. Támas MJ, Hohmann S (2003) The osmotic stress response of Saccharomyces cerevisiae. Topics Curr Genet 1:121-200

    Google Scholar 

  • 53. Tamás MJ, Karlgren S, Bill RM, Hedfalk K, Allegri L, Ferreira M, Thevelein JM, Rydstrom J, Mullins JG, Hohmann S (2003) A short regulatory domain restricts glycerol transport through yeast Fps1p. J Biol Chem 278:6337-6345

    Article  PubMed  Google Scholar 

  • 54. Tyson JJ, Chen KC, Novak B (2003) Sniffers, buzzers, toggles and blinkers: dynamics of regulatory and signaling pathways in the cell. Curr Opin Cell Biol 15:221-231

    Article  PubMed  Google Scholar 

  • 55. van Drogen F, Peter M (2001) MAP kinase dynamics in yeast. Biol Cell 93:63-70

    Article  PubMed  Google Scholar 

  • 56. van Drogen F, Peter M (2002) MAP kinase cascades: scaffolding signal specificity. Curr Biol 12:R53-55

    Article  PubMed  Google Scholar 

  • 57. van Drogen F, Stucke VM, Jorritsma G, Peter M (2001) MAP kinase dynamics in response to pheromones in budding yeast

    Google Scholar 

  • 58. van Drogen F, Stucke VM, Jorritsma G, Peter M (2001) MAP kinase dynamics in response to pheromones in budding yeast. Nat Cell Biol 3:1051-1059

    Article  PubMed  Google Scholar 

  • 59. Vandesompele J, De Preter K, Pattyn F, Poppe B, Van Roy N, De Paepe A, Speleman F (2002) Accurate normalization of real-time quantitative RT-PCR data by geometric averaging of multiple internal control genes. Genome Biol 3:RESEARCH0034

    Article  PubMed  Google Scholar 

  • 60. Wang Y, Ge Q, Houston D, Thorner J, Errede B, Dohlman HG (2003) Regulation of Ste7 ubiquitination by Ste11 phosphorylation and the Skp1-Cullin-F-box complex. J Biol Chem 278:22284-22289

    Article  PubMed  Google Scholar 

  • 61. Versele M, Lemaire K, Thevelein JM (2001) Sex and sugar in yeast: two distinct GPCR systems. EMBO Rep 2:574-579

    Article  PubMed  Google Scholar 

  • 62. 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

    PubMed  Google Scholar 

  • 63. Winson MK, Davey HM (2000) Flow cytometric analysis of microorganisms. Methods 21:231-240

    Article  PubMed  Google Scholar 

  • 64. Wolanin PM, Thomason PA, Stock JB (2002) Histidine protein kinases: key signal transducers outside the animal kingdom. Genome Biol 3:REVIEWS3013

    Article  PubMed  Google Scholar 

  • 65. Yi TM, Kitano H, Simon MI (2003) A quantitative characterization of the yeast heterotrimeric G protein cycle. Proc Natl Acad Sci USA 100:10764-10769

    Article  PubMed  Google Scholar 

  • 66. Zeitlinger J, Simon I, Harbison CT, Hannett NM, Volkert TL, Fink GR, Young RA (2003) Program-specific distribution of a transcription factor dependent on partner transcription factor and MAPK signaling. Cell 113:395-404

    Article  PubMed  Google Scholar 

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Lila Alberghina H.V. Westerhoff

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Nordlander, B., Klipp, E., Kofahl, B., Hohmann, S. Modelling signalling pathways – a yeast approach. In: Alberghina, L., Westerhoff, H. (eds) Systems Biology. Topics in Current Genetics, vol 13. Springer, Berlin, Heidelberg. https://doi.org/10.1007/b106656

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