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. 2001 Apr;157(4):1523–1530. doi: 10.1093/genetics/157.4.1523

A potential phosphorylation site for an A-type kinase in the Efg1 regulator protein contributes to hyphal morphogenesis of Candida albicans.

D P Bockmühl 1, J F Ernst 1
PMCID: PMC1461612  PMID: 11290709

Abstract

Efg1p in the human fungal pathogen Candida albicans is a member of the conserved APSES class of proteins regulating morphogenetic processes in fungi. We have analyzed the importance for hyphal morphogenesis of a putative phosphorylation site for protein kinase A (PKA), threonine-206, within an Efg1p domain highly conserved among APSES proteins. Alanine substitution of T206, but not of the adjacent T207 and T208 residues, led to a block of hypha formation on solid and in liquid media, while a T206E exchange caused hyperfilamentation. The extent of the morphogenetic defect caused by the T206A mutation depended on hypha-induction conditions. Extragenous suppression of mutations in signaling components, including tpk2 and cek1 mutations, was achieved by wild-type- and T206E-, but not by the T206A-variant-encoding allele of EFG1. All muteins tested were produced at equal levels and at high production levels supported pseudohyphal formation. The results are consistent with a role of Efg1p as a central downstream component of a PKA-signaling pathway including Tpk2p or other PKA isoforms. Threonine-206 of Efg1p is essential as a putative phosphorylation target to promote hyphal induction by a subset of environmental cues.

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Selected References

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  1. Aramayo R., Peleg Y., Addison R., Metzenberg R. Asm-1+, a Neurospora crassa gene related to transcriptional regulators of fungal development. Genetics. 1996 Nov;144(3):991–1003. doi: 10.1093/genetics/144.3.991. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Brown D. H., Jr, Giusani A. D., Chen X., Kumamoto C. A. Filamentous growth of Candida albicans in response to physical environmental cues and its regulation by the unique CZF1 gene. Mol Microbiol. 1999 Nov;34(4):651–662. doi: 10.1046/j.1365-2958.1999.01619.x. [DOI] [PubMed] [Google Scholar]
  3. Cannon R. D., Jenkinson H. F., Shepherd M. G. Cloning and expression of Candida albicans ADE2 and proteinase genes on a replicative plasmid in C. albicans and in Saccharomyces cerevisiae. Mol Gen Genet. 1992 Nov;235(2-3):453–457. doi: 10.1007/BF00279393. [DOI] [PubMed] [Google Scholar]
  4. Csank C., Schröppel K., Leberer E., Harcus D., Mohamed O., Meloche S., Thomas D. Y., Whiteway M. Roles of the Candida albicans mitogen-activated protein kinase homolog, Cek1p, in hyphal development and systemic candidiasis. Infect Immun. 1998 Jun;66(6):2713–2721. doi: 10.1128/iai.66.6.2713-2721.1998. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Dutton J. R., Johns S., Miller B. L. StuAp is a sequence-specific transcription factor that regulates developmental complexity in Aspergillus nidulans. EMBO J. 1997 Sep 15;16(18):5710–5721. doi: 10.1093/emboj/16.18.5710. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Ernst J. F. Transcription factors in Candida albicans - environmental control of morphogenesis. Microbiology. 2000 Aug;146(Pt 8):1763–1774. doi: 10.1099/00221287-146-8-1763. [DOI] [PubMed] [Google Scholar]
  7. Feng Q., Summers E., Guo B., Fink G. Ras signaling is required for serum-induced hyphal differentiation in Candida albicans. J Bacteriol. 1999 Oct;181(20):6339–6346. doi: 10.1128/jb.181.20.6339-6346.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Fonzi W. A., Irwin M. Y. Isogenic strain construction and gene mapping in Candida albicans. Genetics. 1993 Jul;134(3):717–728. doi: 10.1093/genetics/134.3.717. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Gimeno C. J., Fink G. R. Induction of pseudohyphal growth by overexpression of PHD1, a Saccharomyces cerevisiae gene related to transcriptional regulators of fungal development. Mol Cell Biol. 1994 Mar;14(3):2100–2112. doi: 10.1128/mcb.14.3.2100. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Gimeno C. J., Ljungdahl P. O., Styles C. A., Fink G. R. Unipolar cell divisions in the yeast S. cerevisiae lead to filamentous growth: regulation by starvation and RAS. Cell. 1992 Mar 20;68(6):1077–1090. doi: 10.1016/0092-8674(92)90079-r. [DOI] [PubMed] [Google Scholar]
  11. Kreegipuu A., Blom N., Brunak S. PhosphoBase, a database of phosphorylation sites: release 2.0. Nucleic Acids Res. 1999 Jan 1;27(1):237–239. doi: 10.1093/nar/27.1.237. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Leuker C. E., Sonneborn A., Delbrück S., Ernst J. F. Sequence and promoter regulation of the PCK1 gene encoding phosphoenolpyruvate carboxykinase of the fungal pathogen Candida albicans. Gene. 1997 Jun 19;192(2):235–240. doi: 10.1016/s0378-1119(97)00069-3. [DOI] [PubMed] [Google Scholar]
  13. Liu H., Köhler J., Fink G. R. Suppression of hyphal formation in Candida albicans by mutation of a STE12 homolog. Science. 1994 Dec 9;266(5191):1723–1726. doi: 10.1126/science.7992058. [DOI] [PubMed] [Google Scholar]
  14. Lo H. J., Köhler J. R., DiDomenico B., Loebenberg D., Cacciapuoti A., Fink G. R. Nonfilamentous C. albicans mutants are avirulent. Cell. 1997 Sep 5;90(5):939–949. doi: 10.1016/s0092-8674(00)80358-x. [DOI] [PubMed] [Google Scholar]
  15. Miller K. Y., Wu J., Miller B. L. StuA is required for cell pattern formation in Aspergillus. Genes Dev. 1992 Sep;6(9):1770–1782. doi: 10.1101/gad.6.9.1770. [DOI] [PubMed] [Google Scholar]
  16. Mösch H. U., Roberts R. L., Fink G. R. Ras2 signals via the Cdc42/Ste20/mitogen-activated protein kinase module to induce filamentous growth in Saccharomyces cerevisiae. Proc Natl Acad Sci U S A. 1996 May 28;93(11):5352–5356. doi: 10.1073/pnas.93.11.5352. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Pan X., Heitman J. Cyclic AMP-dependent protein kinase regulates pseudohyphal differentiation in Saccharomyces cerevisiae. Mol Cell Biol. 1999 Jul;19(7):4874–4887. doi: 10.1128/mcb.19.7.4874. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Pearson R. B., Kemp B. E. Protein kinase phosphorylation site sequences and consensus specificity motifs: tabulations. Methods Enzymol. 1991;200:62–81. doi: 10.1016/0076-6879(91)00127-i. [DOI] [PubMed] [Google Scholar]
  19. Rademacher F., Kehren V., Stoldt V. R., Ernst J. F. A Candida albicans chaperonin subunit (CaCct8p) as a suppressor of morphogenesis and Ras phenotypes in C. albicans and Saccharomyces cerevisiae. Microbiology. 1998 Nov;144(Pt 11):2951–2960. doi: 10.1099/00221287-144-11-2951. [DOI] [PubMed] [Google Scholar]
  20. Riggle P. J., Andrutis K. A., Chen X., Tzipori S. R., Kumamoto C. A. Invasive lesions containing filamentous forms produced by a Candida albicans mutant that is defective in filamentous growth in culture. Infect Immun. 1999 Jul;67(7):3649–3652. doi: 10.1128/iai.67.7.3649-3652.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Robertson L. S., Fink G. R. The three yeast A kinases have specific signaling functions in pseudohyphal growth. Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13783–13787. doi: 10.1073/pnas.95.23.13783. [DOI] [PMC free article] [PubMed] [Google Scholar]
  22. Sonneborn A., Bockmühl D. P., Ernst J. F. Chlamydospore formation in Candida albicans requires the Efg1p morphogenetic regulator. Infect Immun. 1999 Oct;67(10):5514–5517. doi: 10.1128/iai.67.10.5514-5517.1999. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Sonneborn A., Bockmühl D. P., Gerads M., Kurpanek K., Sanglard D., Ernst J. F. Protein kinase A encoded by TPK2 regulates dimorphism of Candida albicans. Mol Microbiol. 2000 Jan;35(2):386–396. doi: 10.1046/j.1365-2958.2000.01705.x. [DOI] [PubMed] [Google Scholar]
  24. Stoldt V. R., Sonneborn A., Leuker C. E., Ernst J. F. Efg1p, an essential regulator of morphogenesis of the human pathogen Candida albicans, is a member of a conserved class of bHLH proteins regulating morphogenetic processes in fungi. EMBO J. 1997 Apr 15;16(8):1982–1991. doi: 10.1093/emboj/16.8.1982. [DOI] [PMC free article] [PubMed] [Google Scholar]

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