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. 1993 Sep;13(9):5659–5669. doi: 10.1128/mcb.13.9.5659

Far1 and Fus3 link the mating pheromone signal transduction pathway to three G1-phase Cdc28 kinase complexes.

M Tyers 1, B Futcher 1
PMCID: PMC360296  PMID: 8395009

Abstract

In the yeast Saccharomyces cerevisiae, the Cdc28 protein kinase controls commitment to cell division at Start, but no biologically relevant G1-phase substrates have been identified. We have studied the kinase complexes formed between Cdc28 and each of the G1 cyclins Cln1, Cln2, and Cln3. Each complex has a specific array of coprecipitated in vitro substrates. We identify one of these as Far1, a protein required for pheromone-induced arrest at Start. Treatment with alpha-factor induces a preferential association and/or phosphorylation of Far1 by the Cln1, Cln2, and Cln3 kinase complexes. This induced interaction depends upon the Fus3 protein kinase, a mitogen-activated protein kinase homolog that functions near the bottom of the alpha-factor signal transduction pathway. Thus, we trace a path through which a mitogen-activated protein kinase regulates a Cdc2 kinase.

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Selected References

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

  1. Becker D. M., Guarente L. High-efficiency transformation of yeast by electroporation. Methods Enzymol. 1991;194:182–187. doi: 10.1016/0076-6879(91)94015-5. [DOI] [PubMed] [Google Scholar]
  2. Boulton T. G., Yancopoulos G. D., Gregory J. S., Slaughter C., Moomaw C., Hsu J., Cobb M. H. An insulin-stimulated protein kinase similar to yeast kinases involved in cell cycle control. Science. 1990 Jul 6;249(4964):64–67. doi: 10.1126/science.2164259. [DOI] [PubMed] [Google Scholar]
  3. Cairns B. R., Ramer S. W., Kornberg R. D. Order of action of components in the yeast pheromone response pathway revealed with a dominant allele of the STE11 kinase and the multiple phosphorylation of the STE7 kinase. Genes Dev. 1992 Jul;6(7):1305–1318. doi: 10.1101/gad.6.7.1305. [DOI] [PubMed] [Google Scholar]
  4. Chang F., Herskowitz I. Identification of a gene necessary for cell cycle arrest by a negative growth factor of yeast: FAR1 is an inhibitor of a G1 cyclin, CLN2. Cell. 1990 Nov 30;63(5):999–1011. doi: 10.1016/0092-8674(90)90503-7. [DOI] [PubMed] [Google Scholar]
  5. Chang F., Herskowitz I. Phosphorylation of FAR1 in response to alpha-factor: a possible requirement for cell-cycle arrest. Mol Biol Cell. 1992 Apr;3(4):445–450. doi: 10.1091/mbc.3.4.445. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Courchesne W. E., Kunisawa R., Thorner J. A putative protein kinase overcomes pheromone-induced arrest of cell cycling in S. cerevisiae. Cell. 1989 Sep 22;58(6):1107–1119. doi: 10.1016/0092-8674(89)90509-6. [DOI] [PubMed] [Google Scholar]
  7. Cross F. R. DAF1, a mutant gene affecting size control, pheromone arrest, and cell cycle kinetics of Saccharomyces cerevisiae. Mol Cell Biol. 1988 Nov;8(11):4675–4684. doi: 10.1128/mcb.8.11.4675. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Dolan J. W., Fields S. Overproduction of the yeast STE12 protein leads to constitutive transcriptional induction. Genes Dev. 1990 Apr;4(4):492–502. doi: 10.1101/gad.4.4.492. [DOI] [PubMed] [Google Scholar]
  9. Elion E. A., Brill J. A., Fink G. R. FUS3 represses CLN1 and CLN2 and in concert with KSS1 promotes signal transduction. Proc Natl Acad Sci U S A. 1991 Nov 1;88(21):9392–9396. doi: 10.1073/pnas.88.21.9392. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Elion E. A., Grisafi P. L., Fink G. R. FUS3 encodes a cdc2+/CDC28-related kinase required for the transition from mitosis into conjugation. Cell. 1990 Feb 23;60(4):649–664. doi: 10.1016/0092-8674(90)90668-5. [DOI] [PubMed] [Google Scholar]
  11. Errede B., Gartner A., Zhou Z., Nasmyth K., Ammerer G. MAP kinase-related FUS3 from S. cerevisiae is activated by STE7 in vitro. Nature. 1993 Mar 18;362(6417):261–264. doi: 10.1038/362261a0. [DOI] [PubMed] [Google Scholar]
  12. Errede B., Levin D. E. A conserved kinase cascade for MAP kinase activation in yeast. Curr Opin Cell Biol. 1993 Apr;5(2):254–260. doi: 10.1016/0955-0674(93)90112-4. [DOI] [PubMed] [Google Scholar]
  13. Field J., Nikawa J., Broek D., MacDonald B., Rodgers L., Wilson I. A., Lerner R. A., Wigler M. Purification of a RAS-responsive adenylyl cyclase complex from Saccharomyces cerevisiae by use of an epitope addition method. Mol Cell Biol. 1988 May;8(5):2159–2165. doi: 10.1128/mcb.8.5.2159. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Fujimura H. Identification and characterization of a mutation affecting the division arrest signaling of the pheromone response pathway in Saccharomyces cerevisiae. Genetics. 1990 Feb;124(2):275–282. doi: 10.1093/genetics/124.2.275. [DOI] [PMC free article] [PubMed] [Google Scholar]
  15. Fujimura H. Molecular cloning of the DAC2/FUS3 gene essential for pheromone-induced G1-arrest of the cell cycle in Saccharomyces cerevisiae. Curr Genet. 1990 Dec;18(5):395–400. doi: 10.1007/BF00309907. [DOI] [PubMed] [Google Scholar]
  16. Gartner A., Nasmyth K., Ammerer G. Signal transduction in Saccharomyces cerevisiae requires tyrosine and threonine phosphorylation of FUS3 and KSS1. Genes Dev. 1992 Jul;6(7):1280–1292. doi: 10.1101/gad.6.7.1280. [DOI] [PubMed] [Google Scholar]
  17. Hadwiger J. A., Wittenberg C., Richardson H. E., de Barros Lopes M., Reed S. I. A family of cyclin homologs that control the G1 phase in yeast. Proc Natl Acad Sci U S A. 1989 Aug;86(16):6255–6259. doi: 10.1073/pnas.86.16.6255. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Ito H., Fukuda Y., Murata K., Kimura A. Transformation of intact yeast cells treated with alkali cations. J Bacteriol. 1983 Jan;153(1):163–168. doi: 10.1128/jb.153.1.163-168.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  19. Lee M. G., Nurse P. Complementation used to clone a human homologue of the fission yeast cell cycle control gene cdc2. Nature. 1987 May 7;327(6117):31–35. doi: 10.1038/327031a0. [DOI] [PubMed] [Google Scholar]
  20. Marsh L., Neiman A. M., Herskowitz I. Signal transduction during pheromone response in yeast. Annu Rev Cell Biol. 1991;7:699–728. doi: 10.1146/annurev.cb.07.110191.003411. [DOI] [PubMed] [Google Scholar]
  21. Nash R., Tokiwa G., Anand S., Erickson K., Futcher A. B. The WHI1+ gene of Saccharomyces cerevisiae tethers cell division to cell size and is a cyclin homolog. EMBO J. 1988 Dec 20;7(13):4335–4346. doi: 10.1002/j.1460-2075.1988.tb03332.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Ogas J., Andrews B. J., Herskowitz I. Transcriptional activation of CLN1, CLN2, and a putative new G1 cyclin (HCS26) by SWI4, a positive regulator of G1-specific transcription. Cell. 1991 Sep 6;66(5):1015–1026. doi: 10.1016/0092-8674(91)90445-5. [DOI] [PubMed] [Google Scholar]
  23. Peter M., Gartner A., Horecka J., Ammerer G., Herskowitz I. FAR1 links the signal transduction pathway to the cell cycle machinery in yeast. Cell. 1993 May 21;73(4):747–760. doi: 10.1016/0092-8674(93)90254-n. [DOI] [PubMed] [Google Scholar]
  24. Reed S. I., Hadwiger J. A., Lörincz A. T. Protein kinase activity associated with the product of the yeast cell division cycle gene CDC28. Proc Natl Acad Sci U S A. 1985 Jun;82(12):4055–4059. doi: 10.1073/pnas.82.12.4055. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. Richardson H. E., Wittenberg C., Cross F., Reed S. I. An essential G1 function for cyclin-like proteins in yeast. Cell. 1989 Dec 22;59(6):1127–1133. doi: 10.1016/0092-8674(89)90768-x. [DOI] [PubMed] [Google Scholar]
  26. Stevenson B. J., Rhodes N., Errede B., Sprague G. F., Jr Constitutive mutants of the protein kinase STE11 activate the yeast pheromone response pathway in the absence of the G protein. Genes Dev. 1992 Jul;6(7):1293–1304. doi: 10.1101/gad.6.7.1293. [DOI] [PubMed] [Google Scholar]
  27. Surana U., Robitsch H., Price C., Schuster T., Fitch I., Futcher A. B., Nasmyth K. The role of CDC28 and cyclins during mitosis in the budding yeast S. cerevisiae. Cell. 1991 Apr 5;65(1):145–161. doi: 10.1016/0092-8674(91)90416-v. [DOI] [PubMed] [Google Scholar]
  28. Tyers M., Fitch I., Tokiwa G., Dahmann C., Nash R., Linskens M., Futcher B. Characterization of G1 and mitotic cyclins of budding yeast. Cold Spring Harb Symp Quant Biol. 1991;56:21–32. doi: 10.1101/sqb.1991.056.01.005. [DOI] [PubMed] [Google Scholar]
  29. Tyers M., Tokiwa G., Futcher B. Comparison of the Saccharomyces cerevisiae G1 cyclins: Cln3 may be an upstream activator of Cln1, Cln2 and other cyclins. EMBO J. 1993 May;12(5):1955–1968. doi: 10.1002/j.1460-2075.1993.tb05845.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Tyers M., Tokiwa G., Nash R., Futcher B. The Cln3-Cdc28 kinase complex of S. cerevisiae is regulated by proteolysis and phosphorylation. EMBO J. 1992 May;11(5):1773–1784. doi: 10.1002/j.1460-2075.1992.tb05229.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  31. Valdivieso M. H., Sugimoto K., Jahng K. Y., Fernandes P. M., Wittenberg C. FAR1 is required for posttranscriptional regulation of CLN2 gene expression in response to mating pheromone. Mol Cell Biol. 1993 Feb;13(2):1013–1022. doi: 10.1128/mcb.13.2.1013. [DOI] [PMC free article] [PubMed] [Google Scholar]
  32. Wittenberg C., Sugimoto K., Reed S. I. G1-specific cyclins of S. cerevisiae: cell cycle periodicity, regulation by mating pheromone, and association with the p34CDC28 protein kinase. Cell. 1990 Jul 27;62(2):225–237. doi: 10.1016/0092-8674(90)90361-h. [DOI] [PubMed] [Google Scholar]
  33. Zhou Z., Gartner A., Cade R., Ammerer G., Errede B. Pheromone-induced signal transduction in Saccharomyces cerevisiae requires the sequential function of three protein kinases. Mol Cell Biol. 1993 Apr;13(4):2069–2080. doi: 10.1128/mcb.13.4.2069. [DOI] [PMC free article] [PubMed] [Google Scholar]

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