Home LiteratureArticle Details
PMID: 15456892 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't Research Support, U.S. Gov't, P.H.S.

Persistent activation by constitutive Ste7 promotes Kss1-mediated invasive growth but fails to support Fus3-dependent mating in yeast.

Molecular and cellular biology ·Vol. 24 ·No. 20 ·2004-10-00 ·Pages 9221-38

Maleri S, Ge Q, Hackett EA, Wang Y, Dohlman HG, Errede B

Abstract

Mitogen-activated protein kinase kinase kinase-Ste11 (MAPKKK-Ste11), MAPKK-Ste7, and MAPK-Kss1 mediate pheromone-induced mating differentiation and nutrient-responsive invasive growth in Saccharomyces cerevisiae. The mating pathway also requires the scaffold-Ste5 and the additional MAPK-Fus3. One contribution to specificity in this system is thought to come from stimulus-dependent recruitment of the MAPK cascade to upstream activators that are unique to one or the other pathway. To test this premise, we asked if stimulus-independent signaling by constitutive Ste7 would lead to a loss of biological specificity. Instead, we found that constitutive Ste7 promotes invasion without supporting mating responses. This specificity occurs because constitutive Ste7 activates Kss1, but not Fus3, in vivo and promotes filamentation gene expression while suppressing mating gene expression. Differences in the ability of constitutive Ste7 variants to bind the MAPKs and Ste5 account for the selective activation of Kss1. These findings support the model that Fus3 activation in vivo requires binding to both Ste7 and the scaffold-Ste5 but that Kss1 activation is independent of Ste5. This scaffold-independent activation of Kss1 by constitutive Ste7 and the existence of mechanisms for pathway-specific promoter discrimination impose a unique developmental fate independently of any distinguishing external stimuli.

MeSH Terms
Adaptor Proteins, Signal Transducing/genetics,metabolism Enzyme Activation Feedback, Physiological Gene Expression Regulation, Fungal Genes, Reporter Isoenzymes/genetics,metabolism MAP Kinase Signaling System/physiology Mitogen-Activated Protein Kinase Kinases Mitogen-Activated Protein Kinases/genetics,metabolism Phenotype Pheromones/metabolism Phosphorylation Protein Kinases/genetics,metabolism Recombinant Fusion Proteins/genetics,metabolism Saccharomyces cerevisiae/genetics,growth & development,physiology Saccharomyces cerevisiae Proteins/genetics,metabolism Ubiquitin/metabolism
Chemicals
Adaptor Proteins, Signal Transducing Isoenzymes Pheromones Recombinant Fusion Proteins STE5 protein, S cerevisiae Saccharomyces cerevisiae Proteins Ubiquitin Protein Kinases FUS3 protein, S cerevisiae KSS1 protein, S cerevisiae Mitogen-Activated Protein Kinases Mitogen-Activated Protein Kinase Kinases STE7 protein, S cerevisiae
Authors & Affiliations
6 authors, click to expand affiliations / ORCID
Maleri Seth
Department of Biochemistry and Biophysics, CB 7260, 512 ME Jones, University of North Carolina, Chapel Hill, NC 27599-7260, USA.
Ge Qingyuan
Hackett Elizabeth A
Wang Yuqi
Dohlman Henrik G
Errede Beverly
References (58)
58 references, click to expand
  1. Isolation of monoclonal antibodies specific for human c-myc proto-oncogene product.
    Mol Cell Biol. 1985 Dec;5(12):3610-6 PMID: 3915782
  2. Cooperative binding interactions required for function of the Ty1 sterile responsive element.
    Mol Cell Biol. 1997 Aug;17(8):4330-7 PMID: 9234690
  3. Single-step purification of polypeptides expressed in Escherichia coli as fusions with glutathione S-transferase.
    Gene. 1988 Jul 15;67(1):31-40 PMID: 3047011
  4. 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
  5. A system of shuttle vectors and yeast host strains designed for efficient manipulation of DNA in Saccharomyces cerevisiae.
    Genetics. 1989 May;122(1):19-27 PMID: 2659436
  6. The yeast STE12 protein binds to the DNA sequence mediating pheromone induction.
    Proc Natl Acad Sci U S A. 1989 Aug;86(15):5703-7 PMID: 2668945
  7. STE12, a protein involved in cell-type-specific transcription and signal transduction in yeast, is part of protein-DNA complexes.
    Genes Dev. 1989 Sep;3(9):1349-61 PMID: 2558054
  8. FUS3 encodes a cdc2+/CDC28-related kinase required for the transition from mitosis into conjugation.
    Cell. 1990 Feb 23;60(4):649-64 PMID: 2406028
  9. A yeast-Escherichia coli shuttle vector containing the M13 origin of replication.
    Plasmid. 1990 Mar;23(2):159-62 PMID: 2194231
  10. STE11 is a protein kinase required for cell-type-specific transcription and signal transduction in yeast.
    Genes Dev. 1990 Nov;4(11):1862-74 PMID: 2276621
  11. Assay of yeast mating reaction.
    Methods Enzymol. 1991;194:77-93 PMID: 2005823
  12. 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
  13. Signal transduction in Saccharomyces cerevisiae requires tyrosine and threonine phosphorylation of FUS3 and KSS1.
    Genes Dev. 1992 Jul;6(7):1280-92 PMID: 1628831
  14. Pheromone-induced signal transduction in Saccharomyces cerevisiae requires the sequential function of three protein kinases.
    Mol Cell Biol. 1993 Apr;13(4):2069-80 PMID: 8455599
  15. MAP kinase-related FUS3 from S. cerevisiae is activated by STE7 in vitro.
    Nature. 1993 Mar 18;362(6417):261-4 PMID: 8384702
  16. FUS3 phosphorylates multiple components of the mating signal transduction cascade: evidence for STE12 and FAR1.
    Mol Biol Cell. 1993 May;4(5):495-510 PMID: 8334305
  17. Vectors for the inducible overexpression of glutathione S-transferase fusion proteins in yeast.
    Yeast. 1993 Jul;9(7):715-22 PMID: 8368005
  18. MSG5, a novel protein phosphatase promotes adaptation to pheromone response in S. cerevisiae.
    EMBO J. 1994 Jan 1;13(1):61-70 PMID: 8306972
  19. Activation of MEK family kinases requires phosphorylation of two conserved Ser/Thr residues.
    EMBO J. 1994 Mar 1;13(5):1123-31 PMID: 8131746
  20. Involvement of SRE element of Ty1 transposon in TEC1-dependent transcriptional activation.
    Nucleic Acids Res. 1994 Mar 25;22(6):999-1005 PMID: 8152932
  21. 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
  22. MAP kinases with distinct inhibitory functions impart signaling specificity during yeast differentiation.
    Cell. 1997 Nov 28;91(5):673-84 PMID: 9393860
  23. The Hog1 MAPK prevents cross talk between the HOG and pheromone response MAPK pathways in Saccharomyces cerevisiae.
    Genes Dev. 1998 Sep 15;12(18):2874-86 PMID: 9744864
  24. 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
  25. Relative dependence of different outputs of the Saccharomyces cerevisiae pheromone response pathway on the MAP kinase Fus3p.
    Genetics. 1999 Apr;151(4):1425-44 PMID: 10101167
  26. A PP2A regulatory subunit positively regulates Ras-mediated signaling during Caenorhabditis elegans vulval induction.
    Genes Dev. 1999 Oct 1;13(19):2562-9 PMID: 10521400
  27. Interaction with Tap42 is required for the essential function of Sit4 and type 2A phosphatases.
    Mol Biol Cell. 2003 Nov;14(11):4342-51 PMID: 14551259
  28. Activation of the Saccharomyces cerevisiae filamentation/invasion pathway by osmotic stress in high-osmolarity glycogen pathway mutants.
    Genetics. 1999 Nov;153(3):1091-103 PMID: 10545444
  29. Signaling and circuitry of multiple MAPK pathways revealed by a matrix of global gene expression profiles.
    Science. 2000 Feb 4;287(5454):873-80 PMID: 10657304
  30. Phosphorylation of the MEKK Ste11p by the PAK-like kinase Ste20p is required for MAP kinase signaling in vivo.
    Curr Biol. 2000 Jun 1;10(11):630-9 PMID: 10837245
  31. A conserved docking site in MEKs mediates high-affinity binding to MAP kinases and cooperates with a scaffold protein to enhance signal transmission.
    J Biol Chem. 2001 Mar 30;276(13):10374-86 PMID: 11134045
  32. MAPK specificity in the yeast pheromone response independent of transcriptional activation.
    Curr Biol. 2001 Aug 21;11(16):1266-71 PMID: 11525741
  33. Specificity of MAP kinase signaling in yeast differentiation involves transient versus sustained MAPK activation.
    Mol Cell. 2001 Sep;8(3):683-91 PMID: 11583629
  34. Regulation of G protein-initiated signal transduction in yeast: paradigms and principles.
    Annu Rev Biochem. 2001;70:703-54 PMID: 11395421
  35. Sensing, signalling and integrating physical processes during Saccharomyces cerevisiae invasive and filamentous growth.
    Microbiology. 2002 Apr;148(Pt 4):893-907 PMID: 11932437
  36. Pheromone-dependent ubiquitination of the mitogen-activated protein kinase kinase Ste7.
    J Biol Chem. 2002 May 3;277(18):15766-72 PMID: 11864977
  37. Pheromone induction promotes Ste11 degradation through a MAPK feedback and ubiquitin-dependent mechanism.
    Proc Natl Acad Sci U S A. 2002 Jul 9;99(14):9160-5 PMID: 12077316
  38. Rewiring MAP kinase pathways using alternative scaffold assembly mechanisms.
    Science. 2003 Feb 14;299(5609):1061-4 PMID: 12511654
  39. Program-specific distribution of a transcription factor dependent on partner transcription factor and MAPK signaling.
    Cell. 2003 May 2;113(3):395-404 PMID: 12732146
  40. Regulation of Ste7 ubiquitination by Ste11 phosphorylation and the Skp1-Cullin-F-box complex.
    J Biol Chem. 2003 Jun 20;278(25):22284-9 PMID: 12668671
  41. Multiple roles of Tap42 in mediating rapamycin-induced transcriptional changes in yeast.
    Mol Cell. 2003 Jun;11(6):1467-78 PMID: 12820961
  42. Reconstitution of a yeast protein kinase cascade in vitro: activation of the yeast MEK homologue STE7 by STE11.
    Proc Natl Acad Sci U S A. 1994 Apr 12;91(8):3398-402 PMID: 8159759
  43. Ste5 tethers multiple protein kinases in the MAP kinase cascade required for mating in S. cerevisiae.
    Cell. 1994 Aug 12;78(3):499-512 PMID: 8062390
  44. 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. 1994 Dec 15;8(24):2974-85 PMID: 8001818
  45. Studies on the transformation of intact yeast cells by the LiAc/SS-DNA/PEG procedure.
    Yeast. 1995 Apr 15;11(4):355-60 PMID: 7785336
  46. Protein phosphatase 2A positively and negatively regulates Ras1-mediated photoreceptor development in Drosophila.
    Genes Dev. 1996 Feb 1;10(3):272-8 PMID: 8595878
  47. 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):5352-6 PMID: 8643578
  48. Feedback regulation of map kinase signal pathways.
    Philos Trans R Soc Lond B Biol Sci. 1996 Feb 29;351(1336):143-8; discussion 148-9 PMID: 8650260
  49. Differential input by Ste5 scaffold and Msg5 phosphatase route a MAPK cascade to multiple outcomes.
    EMBO J. 2004 Jul 7;23(13):2564-76 PMID: 15192700
  50. Fusion of Escherichia coli lacZ to the cytochrome c gene of Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 1981 Apr;78(4):2199-203 PMID: 6264467
  51. One-step gene disruption in yeast.
    Methods Enzymol. 1983;101:202-11 PMID: 6310324
  52. Distinctly regulated tandem upstream activation sites mediate catabolite repression of the CYC1 gene of S. cerevisiae.
    Cell. 1984 Feb;36(2):503-11 PMID: 6319028
  53. Signaling in the yeast pheromone response pathway: specific and high-affinity interaction of the mitogen-activated protein (MAP) kinases Kss1 and Fus3 with the upstream MAP kinase kinase Ste7.
    Mol Cell Biol. 1996 Jul;16(7):3637-50 PMID: 8668180
  54. 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
  55. Combinatorial control required for the specificity of yeast MAPK signaling.
    Science. 1997 Feb 28;275(5304):1314-7 PMID: 9036858
  56. Regulation of the mating pheromone and invasive growth responses in yeast by two MAP kinase substrates.
    Curr Biol. 1997 Apr 1;7(4):228-38 PMID: 9094309
  57. Differential regulation of FUS3 MAP kinase by tyrosine-specific phosphatases PTP2/PTP3 and dual-specificity phosphatase MSG5 in Saccharomyces cerevisiae.
    Genes Dev. 1997 Jul 1;11(13):1690-702 PMID: 9224718
  58. A novel leader peptide which allows efficient secretion of a fragment of human interleukin 1 beta in Saccharomyces cerevisiae.
    EMBO J. 1987 Jan;6(1):229-34 PMID: 3034576
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.24.20.9221-9238.2004
Published
2004-10-00
Pages
9221-38
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC517903
Subset
IM
Grants
NIGMS NIH HHS · R01 GM059167 · United States
NIGMS NIH HHS · GM39852 · United States
NIGMS NIH HHS · GM5059167 · United States
External Links
PubMed source DOI: 10.1128/MCB.24.20.9221-9238.2004 PMC Full Text View journal details
Analysis Services
Analysis Services

Contact

No. 2 Wenbo Road, Zhangqiu District, Jinan, Shandong

Qilu Normal University · Genelibs Bioinformatics Lab

750 Shunhua Rd, Jinan

2F, Bldg F, University Science Park

Tel: 0531-88819269

WeChat Official Account

Follow our WeChat subscription account for real-time updates and the latest in medical and biological research.


Business Email

E-mail: product@genelibs.com

Copyright © 2026.Genelibs Jinan Honghui Biotechnology Co., Ltd. 鲁ICP备20007159号-2