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Genetic evidence for the functional redundancy of the calcineurin-and Mpk1-mediated pathways in the regulation of cellular events important for growth inSaccharomyces cerevisiae

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Abstract

Saccharomyces cerevisiae mutants which exhibit phenotypes (calcium resistance and vanadate sensitivity) similar to those of calcineurin-deficient mutants were isolated. The mutants were classified into four complementation groups (crv1,2,3 and4).crv1 was allelic tocnb1, a mutation in the regulatory subunit of calcineurin. The nucleotide sequences ofCRV2 andCRV3 genes which complemented thecrv2 andcrv3 mutations, respectively, are identical to those ofBCK1/SLK1/SKC1/SSP31 andMPK1/SLT2, respectively, which are both involved in the MAP kinase cascade. A calcineurin-deletion mutation (Δcnb1), which by itself has no detectable effect on growth and morphology, enhanced some phenotypes (slow growth and morphological abnormality) ofcrv2 andcrv3 mutants. These phenotypes ofcrv2 andcrv3 mutants were partially suppressed by Ca2+ or by overproduction of the calcineurin subunits (Cmp2 and Cnb1). Like the calcineurin-deficient mutant,crv2 andcrv3 mutants were defective in recovery from α-factor-induced growth arrest. The defect in recovery of the Δcnb1 mutant was suppressed by overexpression ofMPK1. These results indicated that the calcineurin-mediated and the Mpk1- (Bck1-) mediated signaling pathways act in parallel to regulate functionally redundant cellular events important for growth.

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References

  • Brown JL, Bussey H, Stewart RC (1994) Yeast Skn7p functions in a eukaryotic two-component regulatory pathway. EMBO J 13:5186–5194

    PubMed  Google Scholar 

  • Cardenas ME, Hemenway C, Muir RS, Ye R, Fiorentino D, Heitman J (1994) Immunophilins interact with calcineurin in the absence of exogenous immunosuppressive ligands. EMBO J 13:5944–5957

    PubMed  Google Scholar 

  • Cohen P (1989) The structure and regulation of protein phosphatases. Annu Rev Biochem 58:453–508

    PubMed  Google Scholar 

  • Costigan C, Gehrung S, Snyder M (1992) A synthetic lethal screen identifies SLK1, a novel protein kinase homolog implicated in yeast cell morphogenesis and cell growth. Mol Cell Biol 12:1162–1178

    PubMed  Google Scholar 

  • Cunningham KW, Fink GR (1994) Calcineurin-dependent growth control inSaccharomyces cerevisiae mutants lackingPMC1, a homolog of plasma membrane Ca2+ ATPases. J Cell Biol 124:351–363

    PubMed  Google Scholar 

  • Cyert MS, Thorner J (1992) Regulatory subunit (CNB1 gene product) of yeast Ca2+/calmodulin-dependent phosphoprotein phosphatases is required for adaptation to pheromone. Mol Cell Biol 12:3460–3469

    PubMed  Google Scholar 

  • Cyert MS, Kunisawa R, Kaim D, Thorner J (1991) Yeast has homologs (CNA1 andCNA2 gene products) of mammalian calcineurin, a calmodulin-regulated phosphoprotein phosphatase. Proc Natl Acad Sci USA 88:7376–7380

    PubMed  Google Scholar 

  • Douglas CM, Foor F, Marrinan JA, Morin N, Nielsen JB, Dahl AM, Mazur P, Baginsky W, Li W, El-Sherbeini M, Clemas JA, Mandala SM, Frommer BR, Kurtz MB (1994) TheSaccharomyces cerevisiae FKS1 (ETG1) gene encodes an integral membrane protein which is a subunit of 1,3-β-d-glucan synthase. Proc Natl Acad Sci USA 91:12907–12911

    PubMed  Google Scholar 

  • Eng W-K, Faucette L, McLaughlin MM, Cafferkey R, Koltin Y, Morris RA, Young PR, Johnson RK, Livi GP (1994) The yeastFKS1 gene encodes a novel membrane protein, mutations in which confer FK506 and cyclosporin A hypersensitivity and calcineurin-dependent growth. Gene 151:61–71

    PubMed  Google Scholar 

  • Farcasanu IC, Hirata D, Tsuchiya E, Nishiyama F, Miyakawa T (1995) Protein phosphatase 2B ofSaccharomyces cerevisiae is required for tolerance to manganese, blocking the entry of ions into the cells. Eur J Biochem 232:712–717

    PubMed  Google Scholar 

  • Fields FO, Thorner J (1991) Genetic suppression analysis of the function of a protein kinase C (PKC1 gene product) inSaccharomyces cerevisiae cell cycle progression: theSKC1 d mutations. Cold Spring Harbor Symp Quant Biol 56: 51–60

    PubMed  Google Scholar 

  • Garrett-Engele P, Moilanen B, Cyert MS (1995) Calcineurin, the Ca2+/calmodulindependent protein phosphatase, is essential in yeast mutants with cell integrity defects and in mutants that lack a functional vacuolar H+-ATPase. Mol Cell Biol 15: 4103–4114

    PubMed  Google Scholar 

  • Hirata D, Harada S, Namba H, Miyakawa T (1995) Adaptation to high-salt stress inSaccharomyces cerevisiae is regulated by Ca2+/calmodulin-dependent phosphoprotein phosphatase (calcineurin) and cAMP-dependent protein kinase. Mol Gen Genet 249:257–264

    PubMed  Google Scholar 

  • Inoue SB, Takewaki N, Takasuka T, Mio T, Adachi M, Fujii Y, Miyamoto C, Arisawa M, Furuichi Y, Watanabe T (1995) Characterization and gene cloning of 1,3-β-d-glucan synthase fromSaccharomyces cerevisiae. Eur J Biochem 231:845–854

    PubMed  Google Scholar 

  • Irie K, Araki H, Oshima Y (1991) A new protein kinase, SSP31, modulating theSMP3 gene product involved in plasmid maintenance inSaccharomyces cerevisiae. Gene 108:139–144

    PubMed  Google Scholar 

  • Irie K, Takase M, Lee KS, Levin DE, Araki H, Matsumoto K, Oshima Y (1993)MKK1 andMKK2, which encodeSaccharomyces cerevisiae mitogen-activated protein kinase-kinase homologs, function in the pathway mediated by protein kinase C. Mol Cell Biol 13:3076–3083

    PubMed  Google Scholar 

  • Klee CB, Draetta GF, Hubbard MJ (1988) Calcineurin. Adv Enzymol 61:149–200

    PubMed  Google Scholar 

  • Kuno T, Tanaka H, Mukai H, Chang C-D, Hiraga K, Miyakawa T, Tanaka C (1991) cDNA cloning of a calcineurin B homolog inSaccharomyces cerevisiae. Biochem Biophys Res Commun 180:1159–1163

    PubMed  Google Scholar 

  • Lee KS, Levin DE (1992) Dominant mutations in a gene encoding a putative protein kinase (BCK1) bypass the requirement for aSaccharomyces cerevisiae protein kinase C homolog. Mol Cell Biol 12:172–182

    PubMed  Google Scholar 

  • Lee KS, Irie K, Gotoh Y, Watanabe Y, Araki H, Nishida E, Matsumoto K, Levin DE (1993) A yeast mitogen-activated protein kinase homolog (Mpk1p) mediates signalling by protein kinase C. Mol Cell Biol 13:3067–3075

    PubMed  Google Scholar 

  • Liu J (1993) FK506 and cyclosporin, molecular probes for studying intracellular signal transduction. Immunology Today 14:290–295

    PubMed  Google Scholar 

  • Liu Y, Ishii S, Tokai M, Tsutsumi H, Ohki O, Akada R, Tanaka K, Tsuchiya E, Fukui S, Miyakawa T (1991) TheSaccharomyces cerevisiae genes (CMP1 andCMP2) encoding calmodulin-binding proteins homologous to the catalytic subunit of mammalian protein phosphatase 2B. Mol Gen Genet 227:52–59

    PubMed  Google Scholar 

  • Mazur P, Morin N, Baginsky W, El-Sherbeini M, Clemas JA, Nielsen JB, Foor F (1995) Differential expression and function of two homologous subunits of yeast 1,3-β-d-glucan synthase. Mol Cell Biol 15:5671–5681

    PubMed  Google Scholar 

  • Mazzoni C, Zarzov P, Rambourg A, Mann C (1993) TheSLT2 (MPK1) MAP kinase homolog is involved in polarized cell growth inSaccharomyces cerevisiae. J Cell Biol 123:1821–1833

    PubMed  Google Scholar 

  • Mendoza I, Rubio F, Rodriguez-Navarro A, Pardo JM (1994) The protein phosphatase calcineurin is essential for NaCl tolerance ofSaccharomyces cerevisiae. J Biol Chem 269:879–8796

    PubMed  Google Scholar 

  • Nakamura T, Tsutsumi H, Mukai H, Kuno T, Miyakawa T (1992) Ca2+/calmodulin-activated protein phosphatase (PP2B) ofSaccharomyces cerevisiae: PP2B activity is not essential for growth. FEBS Lett 309:103–106

    PubMed  Google Scholar 

  • Nakamura T, Liu Y, Hirata D, Namba H, Harada S, Hirokawa T, Miyakawa T (1993) Protein phosphatase type 2B (calcineurin)-mediated, FK506-sensitive regulation of intracellular ions in yeast is an important determinant for adaptation to high salt stress conditions. EMBO J 12:4063–4071

    PubMed  Google Scholar 

  • Nakamura T, Namba H, Ohmoto T, Liu Y, Hirata D, Miyakawa T (1995) Cloning and characterization of theSaccharomyces cerevisiae SVS1 gene which encodes a serine- and threonine-rich protein required for vanadate resistance. Gene 165:25–29

    PubMed  Google Scholar 

  • Parent SA, Nielsen JB, Morin N, Chrebet G, Ramadan N, Dahl AM, Hsu M-J, Bostian KA, Foor F (1993) Calcineurin-dependent growth of an FK506- and CsA-hypersensitive mutant ofSaccharomyces cerevisiae. J Gen Microbiol 139:2973–2984

    PubMed  Google Scholar 

  • Posas F, Camps M, Ariño J (1995) The PPZ protein phosphatases are important determinants of salt tolerance in yeast cells. J Biol Chem 270:13036–13041

    PubMed  Google Scholar 

  • Roemer T, Paravicini G, Payton MA, Bussey H (1994) Characterization of the yeast (1,6)-β-glucan biosynthetic components, Kre6p and Skn1p, and genetic interactions between thePKC1 pathway and extracellular matrix assembly. J Cell Biol 127:567–579

    PubMed  Google Scholar 

  • Rothstein RJ (1983) One-step gene distribution in yeast. Methods Enzymol 101:202–211

    PubMed  Google Scholar 

  • Sambrook J, Fritsch EF, Maniatis T (1989) Molecular cloning: a laboratory mannual (2nd edn). Cold Spring Harbor Laboratory Press, Cold Spring Harbor, New York

    Google Scholar 

  • Sherman F, Fink GR, Hicks JB (1986) Methods in yeast genetics. Cold Spring Harbor Laboratory, Cold Spring Harbor, New York

    Google Scholar 

  • Tanida I, Hasegawa A, Iida H, Ohya Y, Anraku Y (1995) Cooperation of calcineurin and vacuolar H+-ATPase in intracellular Ca2+ homeostasis of yeast cells. J Biol Chem 270:10113–10119

    PubMed  Google Scholar 

  • Torres L, Martin H, Garcia-Saez MI, Arroyo J, Molina M, Sanchez M, Nombela C (1991) A protein kinase gene complements the lytic phenotype ofSaccharomyces cerevisiae lyt2 mutants. Mol Microbiol 5:2845–2854

    PubMed  Google Scholar 

  • Yoshida S, Ohya Y, Nakano A, Anraku Y (1994) Genetic interactions among genes involved in theSTT4-PKC1 pathways ofSaccharomyces cerevisiae. Mol Gen Genet 242:631–640

    PubMed  Google Scholar 

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Authors and Affiliations

  1. Department of Fermentation Technology, Faculty of Engineering, Hiroshima University, 739, Higashi-Hiroshima, Japan

    T. Nakamura, T. Ohmoto, D. Hirata, E. Tsuchiya & T. Miyakawa

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  1. T. Nakamura
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  2. T. Ohmoto
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  3. D. Hirata
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  4. E. Tsuchiya
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  5. T. Miyakawa
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Communicated by C. P. Hollenberg

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Nakamura, T., Ohmoto, T., Hirata, D. et al. Genetic evidence for the functional redundancy of the calcineurin-and Mpk1-mediated pathways in the regulation of cellular events important for growth inSaccharomyces cerevisiae . Molec. Gen. Genet. 251, 211–219 (1996). https://doi.org/10.1007/BF02172920

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  • DOI: https://doi.org/10.1007/BF02172920

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