1887

Abstract

The gene encodes a mitogen-activated protein (MAP) kinase, which has been cloned by complementation of the lytic phenotype associated with () mutants. In this work, the physiological role of this MAP kinase in the pathogenic fungus was characterized and a role for in the biogenesis of the cell wall suggested based on the following criteria. First, Δ/Δ strains displayed alterations in their cell surfaces under specific conditions as evidenced by scanning electron microscopy. Second, an increase in specific cell wall epitopes (-glycosylated mannoprotein) was shown by confocal microscopy in Δ/Δ mutants. Third, the sensitivity to antifungals which inhibit (1,3)-β-glucan and chitin synthesis was increased in these mutants. In addition, evidence for a role for the gene in morphological transitions in is presented based on the impairment of pseudohyphal formation of Δ/Δ strains on Spider medium and on the effect of its overexpression on colony morphology on SLADH medium. Using the two-hybrid system, it was also demonstrated that is able to interact specifically with Mkk1p and Mkk2p, the MAP-kinase kinases of the -mediated route of , and to activate transcription in when bound to a DNA-binding element. These results suggest a role for this MAP kinase in the construction of the cell wall of and indicate its potential relevance for the development of novel antifungals.

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1998-02-01
2024-04-25
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References

  1. Arellano M., Durán A., Pérez P. 1996; Rho1 GTPase activates the (l-3)β-D-glucan synthase and is involved in Schizosaccharomyces pombe morphogenesis.. EMBO J 15:4584–4591
    [Google Scholar]
  2. Bardwell L, Cook J. G., Inouye C. J., Thorner J. 1994; Signal propagation and regulation in the mating pheromone response pathway of the yeast Saccharomyces cerevisiae . Dev Biol 166:363–379
    [Google Scholar]
  3. Breeden L., Nasmyth K. 1985; Regulation of the yeast HO gene.. Cold Spring Harbor Symp Quant Biol 50:643–650
    [Google Scholar]
  4. Brewster J. L., de Valoir T., Dwyer N. D., Winter E., Gustin M. C. 1993; An osmosensing signal transduction pathway in yeast.. Science 259:1760–1763
    [Google Scholar]
  5. Cabib E., Duran A. 1975; Simple and sensitive procedure for screening yeast mutants that lyse at non-permissive temperatures.. J Bacteriol 124:1604–1606
    [Google Scholar]
  6. Chen D. C., Yang B. C., Kuo T. T. 1992; One-step transformation of yeast in stationary phase.. Curr Genet 21:83–84
    [Google Scholar]
  7. Clark K. L., Feldmann P. J., Dignard D., Larocque R., Brown A. J. P., Lee M. G., Thomas D. Y., Whiteway M. 1995; Constitutive activation of the Saccharomyces cerevisiae mating response pathway by a MAP kinase kinase from Candida albicans . Mol Gen Genet 249:609–621
    [Google Scholar]
  8. Costigan C., Snyder M. 1994; SLK1, a yeast homolog of MAP kinase activators, has a RAS/cAMP-independent role in nutrient sensing.. Mol Gen Genet 243:286–296
    [Google Scholar]
  9. 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
    [Google Scholar]
  10. Davenport K. R., Sohaskey M., Kamada Y., Levin D. E., Gustin M. C. 1995; A second osmosensing signal transduction pathway in yeast. Hypotonic shock activates the PKC1 protein kinase-regulated cell integrity pathway.. J Biol Cbem 270:30157–30161
    [Google Scholar]
  11. Diez-Orejas R., Molero G., Navarro-García F., Pla J., Nombela C., Sánchez-Pérez M. 1997; Reduced virulence of Candida albicans MKC1 mutants: a role for a mitogen-activated protein kinase in pathogenesis.. Infect Immun 65:833–837
    [Google Scholar]
  12. Drgonová J., Drgon T., Tanaka K., Kollár R., Chen G. C., Ford R. A., Chan C. S., Takai Y., Cabib E. 1996; Rholp, a yeast protein at the interface between cell polarization and morphogenesis.. Science 272:277–279
    [Google Scholar]
  13. Elorza M. V., Rico H., Gozalbo D., Sentandreu R. 1983; Cell wall composition and protoplast regeneration in Candida albicans . Antonie Leeuwenhoek 49:457–469
    [Google Scholar]
  14. Elorza M. V., Mormeneo S., García de la Cruz F., Gimeno C., Sentandreu R. 1989; Evidence for the formation of covalent bonds between macromolecules in the domain of the wall of Candida albicans mycelial cells.. Biochem Biophys Res Commun 162:1118–1125
    [Google Scholar]
  15. Errede B., Levin D. E. 1993; A conserved kinase cascade for MAP kinase activation in yeast.. Curr Opin Cell Biol 5:254–260
    [Google Scholar]
  16. Errede B., Cade R. M., Yashar B. M., Kamada Y., Levin D. E., Irie K., Matsumoto K. 1995; Dynamics and organization of MAP kinase signal pathways.. Mol Reprod Dev 42:477–485
    [Google Scholar]
  17. Fields S., Song O. 1989; A novel genetic system to detect protein-protein interactions.. Nature 340:245–246
    [Google Scholar]
  18. Fonzi W. A., Irwin M. Y. 1993; Isogenic strain construction and gene mapping in Candida albicans . Genetics 134:717–728
    [Google Scholar]
  19. Frost D. J., Brandt K. D., Cugier D., Goldman R. 1995; Awhole-cell Candida albicans assay for the detection of inhibitors towards fungal cell wall synthesis and assembly.. J Antibiot 48:306–310
    [Google Scholar]
  20. de la Fuente J. M., Alvarez A., Nombela C., Sánchez M. 1992; Flow cytometric analysis of Saccharomyces cerevisiae autolytic mutants and protoplasts.. Yeast 8:39–45
    [Google Scholar]
  21. Garrett-Engele P., Moilanen B., Cyert M. S. 1995; Cal- cineurin, the Ca2+/calmodulin-dependent 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
    [Google Scholar]
  22. Gillum A. M., Tsay E. Y. H., Kirsch D. R. 1984; Isolation of the Candida albicans gene for orotidine-5ʹ-phosphate decarboxylase by complementation of S. cerevisiae ura3 and E. coli pyrF mutations.. Mol Gen Genet 198:179–182
    [Google Scholar]
  23. Gimeno C. J., Fink G. R. 1994; Induction of pseudohyphal growth by overexpression of PHD1, a Saccharomyces cerevisiae gene related to transcriptional regulators of fungal development.. Mol Cell Biol 14:2100–2112
    [Google Scholar]
  24. Gimeno C. J., Ljungdahl P. O., Styles C. A., Fink G. R. 1992; Unipolar cell divisions in the yeast S. cerevisiae lead to filamentous growth: regulation by starvation and RAS.. Cell 68:1077–1090
    [Google Scholar]
  25. Hall J. P., Cherkasova V., Elion E. A., Gustin M. C., Winter E. 1996; The osmoregulatory pathway represses mating pathway activity in Saccharomyces cerevisiae: isolation of a FUS3 mutant that is insensitive to the repression mechanism.. Mol Cell Biol 16:6715–6723
    [Google Scholar]
  26. Hanahan D. 1988 Techniques for transformation of E. coli . In DNA Cloning pp 109–135 Edited by Glover D. M. Oxford: IRL Press;
    [Google Scholar]
  27. Herreros E., García-Sáez M. I., Nombela C., Scinchez M. 1992; A reorganized Candida albicans DNA sequence promoting homologous non-integrative genetic transformation.. Mol Microbiol 6:3567–3574
    [Google Scholar]
  28. Herskowitz I. 1995; MAP kinase pathways in yeast: for mating and more.. Cell 80:187–197
    [Google Scholar]
  29. Hill J. E., Myers A. M., Koerner T. J., Tzagoloff A. 1986; Yeast/E.coli shuttle vectors with multiple unique restriction sites.. Yeast 2:163–167
    [Google Scholar]
  30. Igual J. C., Johnson A. L., Johnston L. H. 1996; Coordinated regulation of gene expression by the cell cycle transcription factor SWI4 and the protein kinase C MAP kinase pathway for yeast cell integrity.. EMBO J 15:5001–5013
    [Google Scholar]
  31. Irie K., Takase M., Lee K. S., Levin D. E., Araki H., Matsumoto K., Oshima Y. 1993; MKK1 and MKK2, which encode Saccharomyces cerevisiae mitogen-activated protein kinase- kinase homologs, function in the pathway mediated by protein kinase C.. Mol Cell Biol 13:3076–3083
    [Google Scholar]
  32. Kamada Y., Jung U. S., Piotrowski J., Levin D. E. 1995; Theprotein kinase C-activated MAP kinase pathway of Saccharomyces cerevisiae mediates a novel aspect of the heat shock response.. Genes Dev 9:1559–1571
    [Google Scholar]
  33. Kamada Y., Qadota H., Python C. P., Anraku Y., Ohya Y., Levin D. E. 1996; Activation of yeast protein kinase C by Rhol GTPase.. J Biol Chem 271:9193–9196
    [Google Scholar]
  34. Kapteyn J. C., Montijn R. C., Dijkgraaf G. J., Van den Ende H., Klis F. M. 1995; Covalent association of β-l,3-glucan with β -l,6- glucosylated mannoproteins in cell walls of Candida albicans . J Bacterial 177:3788–3792
    [Google Scholar]
  35. Köhler J., Fink G. R. 1996; Candida albicans strains heterozygous and homozygous for mutations in mitogen-activated protein kinase signaling components have defects in hyphal development.. Proc Natl Acad Sci USA 93:13223–13228
    [Google Scholar]
  36. Kollár R., Petrikov£ E., Ashwell G., Robbins P. W., Cabib E. 1995; Architecture of the yeast cell wall: the linkage between chitin and β (l-3)-glucan.. J Biol Chem 3:1170–1178
    [Google Scholar]
  37. Krisak L., Strich R., Winters R. S., Hall J. P., Mallory M. J., Kreitzer D., Tuan R. S., Winter E. 1994; SMK1, a developmentally regulated MAP kinase, is required for spore wall assembly in Saccharomyces cerevisiae . Genes Dev 8:2151–2161
    [Google Scholar]
  38. Leberer E., Harcus D., Broadbent I. D. 7 other authors 1996; Signal transduction through homologs of the Ste20p and Ste7p protein kinases can trigger hyphal formation in the pathogenic fungus Candida albicans . Proc Natl Acad Sci USA 93:13217–13222
    [Google Scholar]
  39. Lee K. S., Levin D. E. 1992; Dominant mutations in a gene encoding a putative protein kinase (BCK1) bypass the requirement for a Saccharomyces cerevisiae protein kinase C homolog.. Mol Cell Biol 12:172–182
    [Google Scholar]
  40. Lee K., L, Buckley H. R., Campbell C. C. 1975; An amino acid liquid synthetic medium for the development of mycelial and yeast forms of Candida albicans . J Med Vet Mycol 13:148–153
    [Google Scholar]
  41. Lee K. S., Hines L. K., Levin D. E. 1993a; A pair of functionally redundant yeast genes (PPZ1 and PPZ2) encoding type 1-related protein phosphatases function within the PKC1 -mediated pathway.. Mol Cell Biol 13:5843–5853
    [Google Scholar]
  42. Lee K. S., Irie K., Gotoh Y., Watanabe Y., Araki H., Nishida E., Matsumoto K., Levin D. E. 1993b; A yeast mitogen-activated protein kinase homolog (Mpklp) mediates signalling by protein kinase C.. Mol Cell Biol 13:3067–3075
    [Google Scholar]
  43. Levin D. E., Errede B. 1995; The proliferation of MAP kinase signaling pathways in yeast.. Curr Opin Cell Biol 7:197–202
    [Google Scholar]
  44. Levin D. E., Fields F. O., Kunisawa R., Bishop J. M., Thorner J. 1990; A candidate protein kinase C gene, PKC1, is required for the S. cerevisiae cell cycle.. Cell 62:213–224
    [Google Scholar]
  45. Liu H., Styles C. A., Fink G. R. 1993; Elements of the yeast pheromone response pathway required for filamentous growth of diploids.. Science 262:1741–1744
    [Google Scholar]
  46. Liu H., Kohler J., Fink G. R. 1994; Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog.. Science 266:1723–1726
    [Google Scholar]
  47. Madden K., Sheu Y. J., Baetz K., Andrews B., Snyder M. 1997; SBF cell cycle regulator as a target of the yeast PKC-MAP kinase pathway.. Science 275:1781–1784
    [Google Scholar]
  48. Malathi K., Ganesan K., Datta A. 1994; Identification of a putative transcription factor in Candida albicans that can complement the mating defect of Saccharomyces cerevisiae stel2 mutants.. J Biol Chem 269:22945–22951
    [Google Scholar]
  49. Marcilla A., Mormeneo S., Elorza M. V., Mandus J. J., Sentandreu R. 1993; Wall formation by Candida albicans yeast cells: synthesis, secretion and incorporation of two types of mannoproteins.. J Gen Microbiol 139:2985–2993
    [Google Scholar]
  50. Martín H., Arroyo J., Sdnchez M., Molina M., Nombela C. 1993; Activity of the yeast MAP kinase homologue Slt2 is critically required for cell integrity at 37 degrees C.. Mol Gen Genet 241:177–184
    [Google Scholar]
  51. Martín H., Castellanos M. C., Cenamor R., Sánchez M., Molina M., Nombela C. 1996; Molecular and functional characterization of a mutant allele of the mitogen-activated protein- kinase gene SLT2(MPK1) rescued from yeast autolytic mutants.. Curr Genet 29:516–522
    [Google Scholar]
  52. Mazzoni C., Zarzov P., Rambourg A., Mann C. 1993; The SLT2 (MPK1) MAP kinase homolog is involved in polarized cell growth in Saccharomyces cerevisiae . J Cell Biol 123:1821–1833
    [Google Scholar]
  53. Meissner P. S., Sisk W. P., Berman M. L. 1987; Bacteriophage lambda cloning system for the construction of directional cDNA libraries.. Proc Natl Acad Sci USA 84:4171–4175
    [Google Scholar]
  54. Mendoza I., Rubio F., Rodríguez-Navarro A., Pardo J. M. 1994; The protein phosphatase calcineurin is essential for NaCl tolerance of Saccharomyces cerevisiae . J Biol Chem 269:8792–8796
    [Google Scholar]
  55. Miret J. J., Solari A. J., Barderi P. A., Goldemberg S. H. 1992; Polyamines and cell wall organization in Saccharomyces cerevisiae . Yeast 8:1033–1041
    [Google Scholar]
  56. Nakamura T., Ohmoto T., Hirata D., Tsuchiya E., Miyakawa T. 1996; Genetic evidence for the functional redundancy of the calcineurin- and Mpkl-mediated pathways in the regulation of cellular events important for growth in Saccharomyces cerevisiae . Mol Gen Genet 251:211–219
    [Google Scholar]
  57. National Committee for Clinical Laboratory Standards 1992 Reference method for broth dilution antifungal susceptibility testing of yeast. Proposed standard M27-P.. National Committee for Clinical Laboratory Standards; Villanova, PA, USA:
    [Google Scholar]
  58. Navarro-Garcia F., Sdnchez M., Pla J., Nombela C. 1995; Functional characterization of the MKC1 gene of Candida albicans, which encodes a mitogen-activated protein kinase homolog related to cell integrity.. Mol Cell Biol 15:2197–2206
    [Google Scholar]
  59. Nonaka H., Tanaka K., Hirano H., Fujiwara T., Hohno H., Umikawa M., Mino A., Yoshimi T. 1995; A downstream target of RHO1 small GTP-binding protein is PKC1, a homolog of protein kinase C which leads to activation of the MAP kinase cascade in Saccharomyces cerevisiae . EMBO J 14:5931–5938
    [Google Scholar]
  60. Odds F. C. 1988 Candida and Candidosis 2nd edn London: Baillière Tindall;
    [Google Scholar]
  61. Odds F. C. 1994; Candida species and virulence.. ASM News 60:313–318
    [Google Scholar]
  62. Paravicini G., Mendoza A., Antonsson B., Cooper M., Losberger C., Payton M. 1996; The Candida albicans PKC1 gene encodes a protein kinase C homolog necessary for cellular integrity but not dimorphism.. Yeast 12:741–756
    [Google Scholar]
  63. Popolo L., Gilardelli D., Bonfante P., Vai M. 1997; Increase in chitin as an essential response to defects in assembly of cell wall polymers in the ggpl delta mutant of Saccharomyces cerevisiae . J Bacteriol 179:463–469
    [Google Scholar]
  64. Posas F., Casamayor A., Arifto J. 1993; The PPZ protein phosphatases are involved in the maintenance of osmotic stability of yeast cells.. FEBS Lett 318:282–286
    [Google Scholar]
  65. Posas F, Camps M., Arifto J. 1995; The PPZ protein phosphatases are important determinants of salt tolerance in yeast cells.. J Biol Chem 270:13036–13041
    [Google Scholar]
  66. Qadota H., Python C. P., Inoue S. B., Arisawa M., Anraku Y., Zheng Y., Watanabe T., Levin D. E., Ohya Y. 1996; Identification of yeast Rho1p GTPase as a regulatory subunit of l,3-βglucan synthase.. Science 272:279–281
    [Google Scholar]
  67. Roberts R. L., Fink G. R. 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
    [Google Scholar]
  68. Roemer T., Paravicini G., Payton M. A., Bussey H. 1994; Characterization of the yeast (l-6)-β-glucan biosynthetic components, Kre6p and Sknlp, and genetic interactions between the PKC1 pathway and extracellular matrix assembly.. J Cell Biol 127:567–579
    [Google Scholar]
  69. Sanjuán R., Zueco J., Stock R., Font de Mora J., Sentandreu R. 1995; Identification of glucan-mannoprotein complexes in the cell wall of Candida albicans using a monoclonal antibody that reacts with a (l,6)- β-glucan epitope.. Microbiology 141:1545–1551
    [Google Scholar]
  70. Sengar A. S., Markley N. A., Marini N. J., Young D. 1997; Mkh1, a MEK kinase required for cell wall integrity and proper response to osmotic and temperature stress in Schizosaccharo- myces pombe . Mol Cell Biol 17:3508–3519
    [Google Scholar]
  71. Shimizu J., Yoda K., Yamasaki M. 1994; The hypoosmolarity-sensitive phenotype of the Saccharomyces cerevisiae hpo1 mutant is due to a mutation in PKC1, which regulates expression of β -glucanase.. Mol Gen Genet 242:641–648
    [Google Scholar]
  72. Sikorski R. S., Hieter P. 1989; A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA inSaccharomyces cerevisiae.. Genetics 122:19–27
    [Google Scholar]
  73. Singh P., Ganesan K., Malathi K., Ghosh D., Datta A. 1994; ACPR, a STE12 homologue from Candida albicans, is a strong inducer of pseudohyphae in Saccharomyces cerevisiae haploids and diploids.. Biochem Biophys Res Commun 205:1079–1085
    [Google Scholar]
  74. Soler M., Plovins A., Martfn H., Molina M., Nombela C. 1995; Characterization of domains in the yeast MAP kinase Slt2 (Mpkl) required for functional activity and in vivo interaction with protein kinases Mkk1 and Mkk2.. Mol Microbiol 17:833–842
    [Google Scholar]
  75. Sundstrom P. M., Kenny G. E. 1984; Characterization of antigens specific to the surface of germ tubes of Candida albicans by immunofluorescence.. Infect Immun 43:850–855
    [Google Scholar]
  76. Tiedt L. R., Jooste W. R., Hamilton-Attwell V. L. 1987; Technique for preserving aerial fungus structure for scanning electron microscopy.. Trans Br Mycol Soc 88:420–422
    [Google Scholar]
  77. Toda T., Uno I., Ishikawa T. 7 other authors 1985; In yeast, RAS proteins are controlling elements of adenylate cyclase.. Cell 40:27–36
    [Google Scholar]
  78. Toda T., Dhut S., Superti-Furga G., Gotoh Y., Nishida E., Sugiura R., Kuno T. 1996; The fission yeast pmk1+ gene encodes a novel mitogen-activated protein kinase homolog which regulates cell integrity and functions coordinately with the protein kinase C pathway.. Mol Cell Biol 16:6752–6764
    [Google Scholar]
  79. Torres L., Martín H., García-Sáez M. I., Arroyo J., Molina M., Sdnchez M., Nombela C. 1991; A protein kinase gene complements the lytic phenotype of Saccharomyces cerevisiae lytl mutants.. Mol Microbiol 5:2845–2854
    [Google Scholar]
  80. Varela J. C. S., Praekelt U. M., Meacock P. A., Planta R. J., Mager W. H. 1995; The Saccharomyces cerevisiae HSP12 gene is activated by the high-osmolarity glycerol pathway and negatively regulated by protein kinase A.. Mol Cell Biol 15:6232–6245
    [Google Scholar]
  81. Whiteway M., Dignard D., Thomas D. Y. 1992; Dominant negative selection of heterologous genes: isolation of Candida albicans genes that interfere with Saccharomyces cerevisiae mating factor-induced cell cycle arrest.. Proc Natl Acad Sci USA 89:9410–9414
    [Google Scholar]
  82. Williams S., Veldkamp C. 1974; Preparation of fungi for scanning electron microscopy.. Trans Br Mycol Soc 63:409–412
    [Google Scholar]
  83. Zaitsevskaya-Carter T., Cooper J. A. 1997; Spml, a stress-activated MAP kinase that regulates morphogenesis in S. pombe . EMBO J 16:1318–1331
    [Google Scholar]
  84. Zarzov P., Mazzoni C., Mann C. 1996; The SLT2(MPK1) MAP kinase is activated during periods of polarized cell growth in yeast.. EMBO J 15:83–91
    [Google Scholar]
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