Home LiteratureArticle Details
PMID: 7565673 Published · ppublish English Journal Article Research Support, Non-U.S. Gov't

Pheromone signalling in Saccharomyces cerevisiae requires the small GTP-binding protein Cdc42p and its activator CDC24.

Molecular and cellular biology ·Vol. 15 ·No. 10 ·1995-10-00 ·Pages 5246-57

Zhao ZS, Leung T, Manser E, Lim L

Abstract

Pheromone signalling in Saccharomyces cerevisiae is mediated by the STE4-STE18 G-protein beta gamma subunits. A possible target for the subunits is Ste20p, whose structural homolog, the serine/threonine kinase PAK, is activated by GTP-binding p21s Cdc42 and Rac1. The putative Cdc42p-binding domain of Ste20p, expressed as a fusion protein, binds human and yeast GTP-binding Cdc42p. Cdc42p is required for alpha-factor-induced activation of FUS1.cdc24ts strains defective for Cdc42p GDP/GTP exchange show no pheromone induction at restrictive temperatures but are partially rescued by overexpression of Cdc42p, which is potentiated by Cdc42p12V mutants. Epistatic analysis indicates that CDC24 and CDC42 lie between STE4 and STE20 in the pathway. The two-hybrid system revealed that Ste4p interacts with Cdc24p. We propose that Cdc42p plays a pivotal role both in polarization of the cytoskeleton and in pheromone signalling.

Related Genes
CDC24 CDC42 FUS1 STE20 STE4
MeSH Terms
Amino Acid Sequence Base Sequence Cell Cycle Proteins/metabolism Epistasis, Genetic Fungal Proteins/genetics GTP-Binding Protein beta Subunits GTP-Binding Proteins/genetics,metabolism Genes, Fungal Guanine Nucleotide Exchange Factors Heterotrimeric GTP-Binding Proteins Humans Intracellular Signaling Peptides and Proteins MAP Kinase Kinase Kinases Mating Factor Membrane Proteins Molecular Sequence Data Peptides/metabolism,pharmacology Pheromones/metabolism Protein Serine-Threonine Kinases/genetics,metabolism Protein-Tyrosine Kinases/genetics,metabolism Proto-Oncogene Proteins/metabolism Recombinant Fusion Proteins/biosynthesis Saccharomyces cerevisiae/physiology Saccharomyces cerevisiae Proteins Sequence Alignment Signal Transduction/physiology Transcriptional Activation/drug effects cdc42 GTP-Binding Protein, Saccharomyces cerevisiae
Chemicals
CDC24 protein, S cerevisiae Cell Cycle Proteins FUS1 protein, S cerevisiae Fungal Proteins GTP-Binding Protein beta Subunits Guanine Nucleotide Exchange Factors Intracellular Signaling Peptides and Proteins Membrane Proteins Peptides Pheromones Proto-Oncogene Proteins Recombinant Fusion Proteins Saccharomyces cerevisiae Proteins Ste4 protein, S cerevisiae Mating Factor Protein-Tyrosine Kinases Protein Serine-Threonine Kinases MAP Kinase Kinase Kinases STE20 protein, S cerevisiae GTP-Binding Proteins Heterotrimeric GTP-Binding Proteins cdc42 GTP-Binding Protein, Saccharomyces cerevisiae
Authors & Affiliations
4 authors, click to expand affiliations / ORCID
Zhao Z S
Institute of Molecular and Cell Biology, National University of Singapore, Kent Ridge.
Leung T
Manser E
Lim L
References (72)
72 references, click to expand
  1. Ras-dependent activation of MAP kinase pathway mediated by G-protein beta gamma subunits.
    Nature. 1994 Jun 2;369(6479):418-20 PMID: 8196770
  2. The CDC42 homologue from Caenorhabditis elegans. Complementation of yeast mutation.
    J Biol Chem. 1993 Jun 25;268(18):13280-5 PMID: 8514766
  3. Subcellular localization of Cdc42p, a Saccharomyces cerevisiae GTP-binding protein involved in the control of cell polarity.
    Mol Biol Cell. 1993 Dec;4(12):1307-16 PMID: 8167411
  4. Binding of G protein beta gamma-subunits to pleckstrin homology domains.
    J Biol Chem. 1994 Apr 8;269(14):10217-20 PMID: 8144601
  5. Control of the yeast bud-site assembly GTPase Cdc42. Catalysis of guanine nucleotide exchange by Cdc24 and stimulation of GTPase activity by Bem3.
    J Biol Chem. 1994 Jan 28;269(4):2369-72 PMID: 8300560
  6. Conservation and reiteration of a kinase cascade.
    Trends Genet. 1993 Nov;9(11):390-4 PMID: 8310536
  7. Dominant-negative mutants of a yeast G-protein beta subunit identify two functional regions involved in pheromone signalling.
    EMBO J. 1992 Dec;11(13):4805-13 PMID: 1464310
  8. Use of a screen for synthetic lethal and multicopy suppressee mutants to identify two new genes involved in morphogenesis in Saccharomyces cerevisiae.
    Mol Cell Biol. 1991 Mar;11(3):1295-305 PMID: 1996092
  9. Concerted action of RAS and G proteins in the sexual response pathways of Schizosaccharomyces pombe.
    Mol Cell Biol. 1994 Jan;14(1):50-8 PMID: 8264618
  10. A novel genetic system to detect protein-protein interactions.
    Nature. 1989 Jul 20;340(6230):245-6 PMID: 2547163
  11. Requirement for Ras in Raf activation is overcome by targeting Raf to the plasma membrane.
    Nature. 1994 Jun 2;369(6479):411-4 PMID: 8196769
  12. Elements of the yeast pheromone response pathway required for filamentous growth of diploids.
    Science. 1993 Dec 10;262(5140):1741-4 PMID: 8259520
  13. Direct interaction of Ras and the amino-terminal region of Raf-1 in vitro.
    Nature. 1993 Jul 22;364(6435):352-5 PMID: 8332195
  14. Regulation of mating in the cell cycle of Saccharomyces cerevisiae.
    J Cell Biol. 1977 Nov;75(2 Pt 1):355-65 PMID: 400872
  15. The small GTP-binding protein rac regulates growth factor-induced membrane ruffling.
    Cell. 1992 Aug 7;70(3):401-10 PMID: 1643658
  16. Characterization and expression of the human rhoH12 gene product.
    Mol Cell Biol. 1989 May;9(5):2058-66 PMID: 2501657
  17. Overexpression of the STE4 gene leads to mating response in haploid Saccharomyces cerevisiae.
    Mol Cell Biol. 1990 Jan;10(1):217-22 PMID: 2104659
  18. The PH domain: a common piece in the structural patchwork of signalling proteins.
    Trends Biochem Sci. 1993 Sep;18(9):343-8 PMID: 8236453
  19. A dominant truncation allele identifies a gene, STE20, that encodes a putative protein kinase necessary for mating in Saccharomyces cerevisiae.
    Proc Natl Acad Sci U S A. 1993 Jan 15;90(2):452-6 PMID: 8421676
  20. Pheromone response in yeast.
    Bioessays. 1992 Jun;14(6):367-73 PMID: 1323961
  21. Mutational activation of the STE5 gene product bypasses the requirement for G protein beta and gamma subunits in the yeast pheromone response pathway.
    Mol Cell Biol. 1994 Feb;14(2):1054-65 PMID: 8289786
  22. Genetic Control of the Cell Division Cycle in Yeast: V. Genetic Analysis of cdc Mutants.
    Genetics. 1973 Jun;74(2):267-86 PMID: 17248617
  23. 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
  24. A non-receptor tyrosine kinase that inhibits the GTPase activity of p21cdc42.
    Nature. 1993 May 27;363(6427):364-7 PMID: 8497321
  25. Activation of Raf as a result of recruitment to the plasma membrane.
    Science. 1994 Jun 3;264(5164):1463-7 PMID: 7811320
  26. 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
  27. A brain serine/threonine protein kinase activated by Cdc42 and Rac1.
    Nature. 1994 Jan 6;367(6458):40-6 PMID: 8107774
  28. Sexual conjugation in yeast. Cell surface changes in response to the action of mating hormones.
    J Cell Biol. 1979 Feb;80(2):326-33 PMID: 379012
  29. Sex, stress and integrity: the importance of MAP kinases in yeast.
    Curr Opin Genet Dev. 1994 Feb;4(1):90-5 PMID: 8193546
  30. STE50, a novel gene required for activation of conjugation at an early step in mating in Saccharomyces cerevisiae.
    Mol Gen Genet. 1992 Dec;236(1):145-54 PMID: 1494345
  31. Breakpoint cluster region gene product-related domain of n-chimaerin. Discrimination between Rac-binding and GTPase-activating residues by mutational analysis.
    J Biol Chem. 1994 Jul 1;269(26):17642-8 PMID: 8021274
  32. 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
  33. Molecular cloning and expression of a G25K cDNA, the human homolog of the yeast cell cycle gene CDC42.
    Mol Cell Biol. 1990 Nov;10(11):5977-82 PMID: 2122236
  34. Regulation of cytoplasmic division of Xenopus embryo by rho p21 and its inhibitory GDP/GTP exchange protein (rho GDI).
    J Cell Biol. 1993 Mar;120(5):1187-95 PMID: 8436590
  35. Isolation of the Rb-related p130 through its interaction with CDK2 and cyclins.
    Genes Dev. 1993 Dec;7(12A):2378-91 PMID: 8253384
  36. Conjugation in Saccharomyces cerevisiae.
    Annu Rev Cell Biol. 1988;4:429-57 PMID: 2848554
  37. Cdc42p GTPase is involved in controlling polarized cell growth in Schizosaccharomyces pombe.
    Mol Cell Biol. 1994 Feb;14(2):1075-83 PMID: 8289788
  38. Cooperative interaction of S. pombe proteins required for mating and morphogenesis.
    Cell. 1994 Oct 7;79(1):131-41 PMID: 7923372
  39. Multicopy suppression of the cdc24 budding defect in yeast by CDC42 and three newly identified genes including the ras-related gene RSR1.
    Proc Natl Acad Sci U S A. 1989 Dec;86(24):9976-80 PMID: 2690082
  40. Cellular transformation and guanine nucleotide exchange activity are catalyzed by a common domain on the dbl oncogene product.
    J Biol Chem. 1994 Jan 7;269(1):62-5 PMID: 8276860
  41. A conserved kinase cascade for MAP kinase activation in yeast.
    Curr Opin Cell Biol. 1993 Apr;5(2):254-60 PMID: 8389568
  42. Molecular characterization of CDC42, a Saccharomyces cerevisiae gene involved in the development of cell polarity.
    J Cell Biol. 1990 Jul;111(1):143-52 PMID: 2164028
  43. Signal transduction during pheromone response in yeast.
    Annu Rev Cell Biol. 1991;7:699-728 PMID: 1667085
  44. Detection of protein-protein interactions using different vectors in the two-hybrid system.
    Nucleic Acids Res. 1994 Aug 11;22(15):3241-2 PMID: 8065941
  45. A potential positive feedback loop controlling CLN1 and CLN2 gene expression at the start of the yeast cell cycle.
    Cell. 1991 May 31;65(5):875-83 PMID: 2040016
  46. Multifunctional yeast high-copy-number shuttle vectors.
    Gene. 1992 Jan 2;110(1):119-22 PMID: 1544568
  47. LRG1 is expressed during sporulation in Saccharomyces cerevisiae and contains motifs similar to LIM and rho/racGAP domains.
    Nucleic Acids Res. 1994 Aug 11;22(15):3151-4 PMID: 8065929
  48. Complex formation between RAS and RAF and other protein kinases.
    Proc Natl Acad Sci U S A. 1993 Jul 1;90(13):6213-7 PMID: 8327501
  49. Oncogene ect2 is related to regulators of small GTP-binding proteins.
    Nature. 1993 Apr 1;362(6419):462-5 PMID: 8464478
  50. A novel oncogene, ost, encodes a guanine nucleotide exchange factor that potentially links Rho and Rac signaling pathways.
    EMBO J. 1994 Oct 17;13(20):4776-86 PMID: 7957046
  51. Signal transduction during mating and meiosis in S. pombe.
    Trends Cell Biol. 1993 Feb;3(2):60-5 PMID: 14731730
  52. A yeast gene (BEM1) necessary for cell polarization whose product contains two SH3 domains.
    Nature. 1992 Mar 5;356(6364):77-9 PMID: 1538785
  53. Molecular cloning of the gene for the human placental GTP-binding protein Gp (G25K): identification of this GTP-binding protein as the human homolog of the yeast cell-division-cycle protein CDC42.
    Proc Natl Acad Sci U S A. 1990 Dec;87(24):9853-7 PMID: 2124704
  54. Nucleotide sequence of the CLS4 (CDC24) gene of Saccharomyces cerevisiae.
    Gene. 1987;54(1):125-32 PMID: 3301539
  55. Catalysis of guanine nucleotide exchange on the CDC42Hs protein by the dbl oncogene product.
    Nature. 1991 Nov 28;354(6351):311-4 PMID: 1956381
  56. Cloning of Saccharomyces cerevisiae STE5 as a suppressor of a Ste20 protein kinase mutant: structural and functional similarity of Ste5 to Far1.
    Mol Gen Genet. 1993 Nov;241(3-4):241-54 PMID: 8246877
  57. Roles of the CDC24 gene product in cellular morphogenesis during the Saccharomyces cerevisiae cell cycle.
    J Cell Biol. 1981 Jun;89(3):395-405 PMID: 7019215
  58. Mammalian Ras interacts directly with the serine/threonine kinase Raf.
    Cell. 1993 Jul 16;74(1):205-14 PMID: 8334704
  59. A DBL-homologous region of the yeast CLS4/CDC24 gene product is important for Ca(2+)-modulated bud assembly.
    Biochem Biophys Res Commun. 1991 Dec 16;181(2):604-10 PMID: 1755844
  60. MAP kinase kinase kinase, MAP kinase kinase and MAP kinase.
    Curr Opin Genet Dev. 1994 Feb;4(1):82-9 PMID: 8193545
  61. Diversity in function and regulation of MAP kinase pathways.
    Trends Biochem Sci. 1994 Jun;19(6):236-40 PMID: 8073500
  62. The role of CDC28 and cyclins during mitosis in the budding yeast S. cerevisiae.
    Cell. 1991 Apr 5;65(1):145-61 PMID: 1849457
  63. Overproduction of the yeast STE12 protein leads to constitutive transcriptional induction.
    Genes Dev. 1990 Apr;4(4):492-502 PMID: 2193847
  64. The STE4 and STE18 genes of yeast encode potential beta and gamma subunits of the mating factor receptor-coupled G protein.
    Cell. 1989 Feb 10;56(3):467-77 PMID: 2536595
  65. Mutation of the SPS1-encoded protein kinase of Saccharomyces cerevisiae leads to defects in transcription and morphology during spore formation.
    Genes Dev. 1994 Sep 15;8(18):2162-75 PMID: 7958886
  66. The ras1 function of Schizosaccharomyces pombe mediates pheromone-induced transcription.
    EMBO J. 1992 Apr;11(4):1391-5 PMID: 1563351
  67. Diversity and versatility of GTPase activating proteins for the p21rho subfamily of ras G proteins detected by a novel overlay assay.
    J Biol Chem. 1992 Aug 15;267(23):16025-8 PMID: 1644791
  68. 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
  69. ADP-ribosylation of rho p21 inhibits lysophosphatidic acid-induced protein tyrosine phosphorylation and phosphatidylinositol 3-kinase activation in cultured Swiss 3T3 cells.
    J Biol Chem. 1993 Nov 25;268(33):24535-8 PMID: 8227009
  70. The protein kinase homologue Ste20p is required to link the yeast pheromone response G-protein beta gamma subunits to downstream signalling components.
    EMBO J. 1992 Dec;11(13):4815-24 PMID: 1464311
  71. CDC42 and CDC43, two additional genes involved in budding and the establishment of cell polarity in the yeast Saccharomyces cerevisiae.
    J Cell Biol. 1990 Jul;111(1):131-42 PMID: 2195038
  72. High efficiency transformation of intact yeast cells using single stranded nucleic acids as a carrier.
    Curr Genet. 1989 Dec;16(5-6):339-46 PMID: 2692852
Article Info
Journal
Molecular and cellular biology
Abbr.
Mol Cell Biol
ISSN
0270-7306
DOI
10.1128/MCB.15.10.5246
Published
1995-10-00
Pages
5246-57
Language
English
Region
United States
NLM ID
8109087
PMCID
PMC230772
Subset
IM
External Links
PubMed source DOI: 10.1128/MCB.15.10.5246 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: [email protected]

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