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PMID: 12024012 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Protein kinase A operates a molecular switch that governs yeast pseudohyphal differentiation.

Molecular and cellular biology ·Vol. 22 ·No. 12 ·2002-06-00 ·Pages 3981-93

Pan X, Heitman J

Abstract

The yeast Saccharomyces cerevisiae undergoes a dimorphic filamentous transition in response to nutrient cues that is affected by both mitogen-activated protein kinase and cyclic AMP-protein kinase A signaling cascades. Here two transcriptional regulators, Flo8 and Sfl1, are shown to be the direct molecular targets of protein kinase A. Flo8 and Sfl1 antagonistically control expression of the cell adhesin Flo11 via a common promoter element. Phosphorylation by the protein kinase A catalytic subunit Tpk2 promotes Flo8 binding and activation of the Flo11 promoter and relieves repression by prohibiting dimerization and DNA binding by Sfl1. Our studies illustrate in molecular detail how protein kinase A combinatorially effects a key developmental switch. Similar mechanisms may operate in pathogenic fungi and more complex multicellular eukaryotic organisms.

MeSH Terms
Bacterial Proteins/genetics Catalytic Domain Cell Division Cell Nucleus/metabolism Cyclic AMP-Dependent Protein Kinases/metabolism Fungal Proteins/genetics,metabolism Gene Expression Regulation, Fungal Membrane Glycoproteins Membrane Proteins/genetics,metabolism Mutation Nuclear Proteins Phosphorylation Promoter Regions, Genetic Protein Kinases/genetics,metabolism Saccharomyces cerevisiae/cytology,physiology Saccharomyces cerevisiae Proteins/genetics,metabolism Serine Endopeptidases/genetics Trans-Activators/genetics,metabolism Transcription Factors
Chemicals
Bacterial Proteins FLO11 protein, S cerevisiae FLO8 protein, S cerevisaie Fungal Proteins LexA protein, Bacteria Membrane Glycoproteins Membrane Proteins Nuclear Proteins SFL1 protein, S cerevisiae Saccharomyces cerevisiae Proteins Trans-Activators Transcription Factors Protein Kinases Cyclic AMP-Dependent Protein Kinases TPK2 protein, S cerevisiae Serine Endopeptidases
Authors & Affiliations
2 authors, click to expand affiliations / ORCID
Pan Xuewen
Department of Genetics, Howard Hughes Medical Institute, Duke University Medical Center, Durham, North Carolina 27710, USA.
Heitman Joseph
References (54)
54 references, click to expand
  1. Nutritional control of nucleocytoplasmic localization of cAMP-dependent protein kinase catalytic and regulatory subunits in Saccharomyces cerevisiae.
    J Biol Chem. 2000 Jan 14;275(2):1449-56 PMID: 10625697
  2. Design of a leucine zipper coiled coil stabilized 1.4 kcal mol-1 by phosphorylation of a serine in the e position.
    Protein Sci. 1997 Jun;6(6):1273-83 PMID: 9194187
  3. Nonfilamentous C. albicans mutants are avirulent.
    Cell. 1997 Sep 5;90(5):939-49 PMID: 9298905
  4. Inhibitory and activating functions for MAPK Kss1 in the S. cerevisiae filamentous-growth signalling pathway.
    Nature. 1997 Nov 6;390(6655):85-8 PMID: 9363895
  5. Yeast pseudohyphal growth is regulated by GPA2, a G protein alpha homolog.
    EMBO J. 1997 Dec 1;16(23):7008-18 PMID: 9384580
  6. MAP kinases with distinct inhibitory functions impart signaling specificity during yeast differentiation.
    Cell. 1997 Nov 28;91(5):673-84 PMID: 9393860
  7. The cell surface flocculin Flo11 is required for pseudohyphae formation and invasion by Saccharomyces cerevisiae.
    Mol Biol Cell. 1998 Jan;9(1):161-71 PMID: 9436998
  8. Nuclear localization of the C2H2 zinc finger protein Msn2p is regulated by stress and protein kinase A activity.
    Genes Dev. 1998 Feb 15;12(4):586-97 PMID: 9472026
  9. Additional modules for versatile and economical PCR-based gene deletion and modification in Saccharomyces cerevisiae.
    Yeast. 1998 Jul;14(10):953-61 PMID: 9717241
  10. Repression of yeast Ste12 transcription factor by direct binding of unphosphorylated Kss1 MAPK and its regulation by the Ste7 MEK.
    Genes Dev. 1998 Sep 15;12(18):2887-98 PMID: 9744865
  11. Srb/mediator proteins interact functionally and physically with transcriptional repressor Sfl1.
    EMBO J. 1998 Oct 1;17(19):5757-65 PMID: 9755175
  12. The three yeast A kinases have specific signaling functions in pseudohyphal growth.
    Proc Natl Acad Sci U S A. 1998 Nov 10;95(23):13783-7 PMID: 9811878
  13. Control of Swe1p degradation by the morphogenesis checkpoint.
    EMBO J. 1998 Nov 16;17(22):6678-88 PMID: 9822611
  14. Regulators of pseudohyphal differentiation in Saccharomyces cerevisiae identified through multicopy suppressor analysis in ammonium permease mutant strains.
    Genetics. 1998 Dec;150(4):1443-57 PMID: 9832522
  15. Differential regulation of transcription: repression by unactivated mitogen-activated protein kinase Kss1 requires the Dig1 and Dig2 proteins.
    Proc Natl Acad Sci U S A. 1998 Dec 22;95(26):15400-5 PMID: 9860980
  16. MAP kinase and cAMP filamentation signaling pathways converge on the unusually large promoter of the yeast FLO11 gene.
    EMBO J. 1999 Mar 1;18(5):1257-69 PMID: 10064592
  17. Heterologous URA3MX cassettes for gene replacement in Saccharomyces cerevisiae.
    Yeast. 1999 Apr;15(6):507-11 PMID: 10234788
  18. Mapping DNA interaction sites of chromosomal proteins using immunoprecipitation and polymerase chain reaction.
    Methods Enzymol. 1999;304:399-414 PMID: 10372373
  19. Cyclic AMP-dependent protein kinase regulates pseudohyphal differentiation in Saccharomyces cerevisiae.
    Mol Cell Biol. 1999 Jul;19(7):4874-87 PMID: 10373537
  20. HWP1 functions in the morphological development of Candida albicans downstream of EFG1, TUP1, and RBF1.
    J Bacteriol. 1999 Sep;181(17):5273-9 PMID: 10464197
  21. Allosteric proteins and cellular control systems.
    J Mol Biol. 1963 Apr;6:306-29 PMID: 13936070
  22. Protein kinase A encoded by TPK2 regulates dimorphism of Candida albicans.
    Mol Microbiol. 2000 Jan;35(2):386-96 PMID: 10652099
  23. The G protein-coupled receptor gpr1 is a nutrient sensor that regulates pseudohyphal differentiation in Saccharomyces cerevisiae.
    Genetics. 2000 Feb;154(2):609-22 PMID: 10655215
  24. TUP1, CPH1 and EFG1 make independent contributions to filamentation in candida albicans.
    Genetics. 2000 May;155(1):57-67 PMID: 10790384
  25. Sok2 regulates yeast pseudohyphal differentiation via a transcription factor cascade that regulates cell-cell adhesion.
    Mol Cell Biol. 2000 Nov;20(22):8364-72 PMID: 11046133
  26. Signal transduction cascades regulating pseudohyphal differentiation of Saccharomyces cerevisiae.
    Curr Opin Microbiol. 2000 Dec;3(6):567-72 PMID: 11121775
  27. Control of pseudohyphae formation in Saccharomyces cerevisiae.
    FEMS Microbiol Rev. 2001 Jan;25(1):107-23 PMID: 11152942
  28. Coiled coils: a highly versatile protein folding motif.
    Trends Cell Biol. 2001 Feb;11(2):82-8 PMID: 11166216
  29. Calcium, calcineurin, and the control of transcription.
    J Biol Chem. 2001 Jan 26;276(4):2313-6 PMID: 11096121
  30. Sfl1 functions via the co-repressor Ssn6-Tup1 and the cAMP-dependent protein kinase Tpk2.
    J Mol Biol. 2001 Jun 22;309(5):1007-15 PMID: 11399075
  31. Yeast promoters and lacZ fusions designed to study expression of cloned genes in yeast.
    Methods Enzymol. 1983;101:181-91 PMID: 6310321
  32. Dual promoter control of the Escherichia coli lactose operon.
    Cell. 1984 Nov;39(1):173-80 PMID: 6091909
  33. Upstream activation sites of the CYC1 gene of Saccharomyces cerevisiae are active when inverted but not when placed downstream of the "TATA box".
    Proc Natl Acad Sci U S A. 1984 Dec;81(24):7860-4 PMID: 6096863
  34. Mutational analysis of upstream activation sequence 2 of the CYC1 gene of Saccharomyces cerevisiae: a HAP2-HAP3-responsive site.
    Mol Cell Biol. 1988 Feb;8(2):647-54 PMID: 2832731
  35. New yeast-Escherichia coli shuttle vectors constructed with in vitro mutagenized yeast genes lacking six-base pair restriction sites.
    Gene. 1988 Dec 30;74(2):527-34 PMID: 3073106
  36. A novel genetic system to detect protein-protein interactions.
    Nature. 1989 Jul 20;340(6230):245-6 PMID: 2547163
  37. Domains of the SFL1 protein of yeasts are homologous to Myc oncoproteins or yeast heat-shock transcription factor.
    Gene. 1989 Dec 28;85(2):321-8 PMID: 2697640
  38. Getting started with yeast.
    Methods Enzymol. 1991;194:3-21 PMID: 2005794
  39. Tackling the protease problem in Saccharomyces cerevisiae.
    Methods Enzymol. 1991;194:428-53 PMID: 2005802
  40. Ssn6-Tup1 is a general repressor of transcription in yeast.
    Cell. 1992 Feb 21;68(4):709-19 PMID: 1739976
  41. Unipolar cell divisions in the yeast S. cerevisiae lead to filamentous growth: regulation by starvation and RAS.
    Cell. 1992 Mar 20;68(6):1077-90 PMID: 1547504
  42. Phosphorylation of CREB affects its binding to high and low affinity sites: implications for cAMP induced gene transcription.
    EMBO J. 1992 Sep;11(9):3337-46 PMID: 1354612
  43. Cyclic adenosine 3',5'-monophosphate response element binding protein (CREB) and related transcription-activating deoxyribonucleic acid-binding proteins.
    Endocr Rev. 1993 Jun;14(3):269-90 PMID: 8319595
  44. Vectors for the inducible overexpression of glutathione S-transferase fusion proteins in yeast.
    Yeast. 1993 Jul;9(7):715-22 PMID: 8368005
  45. PI 3-kinase is a dual specificity enzyme: autoregulation by an intrinsic protein-serine kinase activity.
    EMBO J. 1994 Feb 1;13(3):522-33 PMID: 8313897
  46. New heterologous modules for classical or PCR-based gene disruptions in Saccharomyces cerevisiae.
    Yeast. 1994 Dec;10(13):1793-808 PMID: 7747518
  47. Gene disruption with PCR products in Saccharomyces cerevisiae.
    Gene. 1995 May 26;158(1):113-7 PMID: 7789793
  48. SOK2 may regulate cyclic AMP-dependent protein kinase-stimulated growth and pseudohyphal development by repressing transcription.
    Mol Cell Biol. 1995 Dec;15(12):6854-63 PMID: 8524252
  49. Muc1, a mucin-like protein that is regulated by Mss10, is critical for pseudohyphal differentiation in yeast.
    Proc Natl Acad Sci U S A. 1996 Aug 6;93(16):8419-24 PMID: 8710886
  50. Saccharomyces cerevisiae S288C has a mutation in FLO8, a gene required for filamentous growth.
    Genetics. 1996 Nov;144(3):967-78 PMID: 8913742
  51. Two novel targets of the MAP kinase Kss1 are negative regulators of invasive growth in the yeast Saccharomyces cerevisiae.
    Genes Dev. 1996 Nov 15;10(22):2831-48 PMID: 8918885
  52. Genomic libraries and a host strain designed for highly efficient two-hybrid selection in yeast.
    Genetics. 1996 Dec;144(4):1425-36 PMID: 8978031
  53. Combinatorial control required for the specificity of yeast MAPK signaling.
    Science. 1997 Feb 28;275(5304):1314-7 PMID: 9036858
  54. Control of filament formation in Candida albicans by the transcriptional repressor TUP1.
    Science. 1997 Jul 4;277(5322):105-9 PMID: 9204892
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.22.12.3981-3993.2002
Published
2002-06-00
Pages
3981-93
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC133872
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.22.12.3981-3993.2002 PMC Full Text View journal details
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