The world's first wiki where authorship really matters (Nature Genetics, 2008). Due credit and reputation for authors. Imagine a global collaborative knowledge base for original thoughts. Search thousands of articles and collaborate with scientists around the globe.

wikigene or wiki gene protein drug chemical gene disease author authorship tracking collaborative publishing evolutionary knowledge reputation system wiki2.0 global collaboration genes proteins drugs chemicals diseases compound
Hoffmann, R. A wiki for the life sciences where authorship matters. Nature Genetics (2008)



Gene Review

STE4  -  Ste4p

Saccharomyces cerevisiae S288c

Synonyms: Guanine nucleotide-binding protein subunit beta, YOR212W, YOR50-2
Welcome! If you are familiar with the subject of this article, you can contribute to this open access knowledge base by deleting incorrect information, restructuring or completely rewriting any text. Read more.

Disease relevance of STE4

  • On the other hand, sterility resulting from deletion of STE4 was not suppressed by the mot2 deletion [1].

High impact information on STE4

  • Sequencing of the cloned genes revealed that the STE4 polypeptide shows extensive homology to the beta subunits of mammalian G proteins, while the STE18 polypeptide shows weak similarity to the gamma subunit of transducin [2].
  • Analysis of double mutants suggests that the STE4 gene product functions after the SCG1 product but before the STE5 product [3].
  • The STE4 and STE18 genes are required for haploid yeast cell mating [2].
  • Ste5 also associates with Ste4, the beta subunit of a heterotrimeric guanine nucleotide-binding protein, potentially linking receptor activation to stimulation of the MAPK cascade [4].
  • STE4 encodes the beta-subunit of a heterotrimeric guanine nucleotide-binding protein (G protein) that is an early and essential component of the pheromone signal transduction pathway [5].

Biological context of STE4

  • Mutations in STE4, 5, 7, and 11 partially reduced the number of binding sites, but this reduction was not sufficient to explain the loss of responsiveness; the products of these genes appear to affect postreceptor steps of the response pathway [6].
  • The slow-growth phenotype manifested by cells carrying STE5Hyp alleles was enhanced by the sst2-1 mutation; this effect was eliminated in ste4 mutants [7].
  • The membrane distribution of Ste4p was unaffected by the ste2 mutation or by down-regulation of the cell-surface receptors [8].
  • In order to identify amino acid residues of Ste4p involved in receptor recognition and/or receptor-G protein coupling, we employed random in vitro mutagenesis and a genetic screening to isolate mutant Ste4p subunits with altered pheromone response [9].
  • We generated a plasmid library containing randomly mutagenized Ste4 ORFs, followed by phenotypic selection of ste4p mutants by altered alpha pheromone response in yeast cells [9].

Anatomical context of STE4

  • We found that the products of the STE4 and STE18 genes are stably associated with plasma membrane as well as with internal membranes and that 30% of the protein pool is not tightly associated with either membrane fraction [8].

Associations of STE4 with chemical compounds

  • This delta C6 mutant acts as a dominant negative because it blocks the growth arresting effect obtained by over-expression of STE4 [10].
  • Here we demonstrate that Ste4 and Ste5 activate Kss1 during IG and in response to multiple stimuli including butanol [11].
  • Ste4 contains a leucine zipper and is capable of homotypic interaction [12].

Physical interactions of STE4

  • The two-hybrid system revealed that Ste4p interacts with Cdc24p [13].
  • The identification of a ste18 mutant indicated that this screen could identify proteins that interact directly with Ste4p [14].
  • In cells with a constitutively activated pheromone response pathway, epitope-tagged Ste4p was coimmunoprecipitated with Ste5p [15].
  • Consistent with these genetic observations, the suppressing form of Syg1p can interact with the STE4 gene product, as determined by a two-hybrid assay [16].
  • Mutation of the Q323 residue of Gpa1p resulted in constitutive activation of the pheromone response pathway and eliminated the ability to interact with Ste4p, consistent with a defect in GTPase activity [17].

Regulatory relationships of STE4

  • GPA1 hyperexpression suppressed the phenotype of STE4 overexpression [18].
  • Overexpression of the STE4 gene product also suppressed the sterility of cells defective in the mating pheromone receptors encoded by the STE2 and STE3 genes [19].
  • However, STE18 was essential for the response, since overexpression of STE4 was unable to activate a response in a ste18 null strain [18].

Other interactions of STE4

  • The cross talk in hog1 mutants induced multiple responses of the pheromone response pathway: induction of a FUS1::lacZ reporter, morphological changes, and mating in ste4 and ste5 mutants [20].
  • However, the phenotypes of the STE5Hyp mutations were less pronounced in ste4 and ste18 mutants, suggesting that the STE5Hyp-generated signal partially depends on the proposed G beta gamma complex [7].
  • Others have provided genetic evidence consistent with an interaction between the SCG1 (GPA1) and STE4 gene products [21].
  • This activation was dependent on Ste4p and Ste18p and partially dependent on Ste20p [14].
  • We also found, in a pull-down assay, that Rho1 associates with GST-Ste4 and that Rho1 is localized to the neck and tip of mating projections [22].

Analytical, diagnostic and therapeutic context of STE4

  • A haploid-specific interaction between the amino terminus of Ste5p and the G protein beta subunit Ste4p was also detected in a two-hybrid assay, and the product of a signaling-defective allele of STE4 was defective in this interaction [15].
  • Sequence analysis of the STE4 locus in the relevant mutant strains revealed seven novel STE4 alleles, each of which was shown to disrupt proper regulation of the pheromone response [23].
  • In this study we used site-directed mutagenesis to create two phosphorylation null (Pho-) alleles of STE4: ste4-T320A/S335A and ste4-T322A/S335A [24].
  • Conversely, overproduction of Sst2 markedly enhanced the rate of recovery from pheromone-induced arrest in the long-term halo bioassay and detectably dampened signaling in a short-term assay of pheromone response (phosphorylation of Ste4, Gbeta subunit) [25].


  1. The yeast MOT2 gene encodes a putative zinc finger protein that serves as a global negative regulator affecting expression of several categories of genes, including mating-pheromone-responsive genes. Irie, K., Yamaguchi, K., Kawase, K., Matsumoto, K. Mol. Cell. Biol. (1994) [Pubmed]
  2. The STE4 and STE18 genes of yeast encode potential beta and gamma subunits of the mating factor receptor-coupled G protein. Whiteway, M., Hougan, L., Dignard, D., Thomas, D.Y., Bell, L., Saari, G.C., Grant, F.J., O'Hara, P., MacKay, V.L. Cell (1989) [Pubmed]
  3. Constitutive mutants in the yeast pheromone response: ordered function of the gene products. Blinder, D., Bouvier, S., Jenness, D.D. Cell (1989) [Pubmed]
  4. Ste5 RING-H2 domain: role in Ste4-promoted oligomerization for yeast pheromone signaling. Inouye, C., Dhillon, N., Thorner, J. Science (1997) [Pubmed]
  5. Constitutive mutants of the protein kinase STE11 activate the yeast pheromone response pathway in the absence of the G protein. Stevenson, B.J., Rhodes, N., Errede, B., Sprague, G.F. Genes Dev. (1992) [Pubmed]
  6. Saccharomyces cerevisiae mutants unresponsive to alpha-factor pheromone: alpha-factor binding and extragenic suppression. Jenness, D.D., Goldman, B.S., Hartwell, L.H. Mol. Cell. Biol. (1987) [Pubmed]
  7. Mutational activation of the STE5 gene product bypasses the requirement for G protein beta and gamma subunits in the yeast pheromone response pathway. Hasson, M.S., Blinder, D., Thorner, J., Jenness, D.D. Mol. Cell. Biol. (1994) [Pubmed]
  8. The G beta gamma complex of the yeast pheromone response pathway. Subcellular fractionation and protein-protein interactions. Hirschman, J.E., De Zutter, G.S., Simonds, W.F., Jenness, D.D. J. Biol. Chem. (1997) [Pubmed]
  9. The Leu-132 of the Ste4(Gbeta) subunit is essential for proper coupling of the G protein with the Ste2 alpha factor receptor during the mating pheromone response in yeast. Ongay-Larios, L., Saviñón-Tejeda, A.L., Williamson, M.J., Durán-Avelar, M., Coria, R. FEBS Lett. (2000) [Pubmed]
  10. STE2/SCG1-dependent inhibition of STE4-induced growth arrest by mutant STE4 delta C6 in the yeast pheromone response pathway. Coria, R., Saviñon-Tejeda, A.L., Birnbaumer, L. FEBS Lett. (1995) [Pubmed]
  11. Differential input by Ste5 scaffold and Msg5 phosphatase route a MAPK cascade to multiple outcomes. Andersson, J., Simpson, D.M., Qi, M., Wang, Y., Elion, E.A. EMBO J. (2004) [Pubmed]
  12. Identification of Ste4 as a potential regulator of Byr2 in the sexual response pathway of Schizosaccharomyces pombe. Barr, M.M., Tu, H., Van Aelst, L., Wigler, M. Mol. Cell. Biol. (1996) [Pubmed]
  13. Pheromone signalling in Saccharomyces cerevisiae requires the small GTP-binding protein Cdc42p and its activator CDC24. Zhao, Z.S., Leung, T., Manser, E., Lim, L. Mol. Cell. Biol. (1995) [Pubmed]
  14. Genetic relationships between the G protein beta gamma complex, Ste5p, Ste20p and Cdc42p: investigation of effector roles in the yeast pheromone response pathway. Akada, R., Kallal, L., Johnson, D.I., Kurjan, J. Genetics (1996) [Pubmed]
  15. Association of the yeast pheromone response G protein beta gamma subunits with the MAP kinase scaffold Ste5p. Whiteway, M.S., Wu, C., Leeuw, T., Clark, K., Fourest-Lieuvin, A., Thomas, D.Y., Leberer, E. Science (1995) [Pubmed]
  16. Truncated forms of a novel yeast protein suppress the lethality of a G protein alpha subunit deficiency by interacting with the beta subunit. Spain, B.H., Koo, D., Ramakrishnan, M., Dzudzor, B., Colicelli, J. J. Biol. Chem. (1995) [Pubmed]
  17. Switch-domain mutations in the Saccharomyces cerevisiae G protein alpha-subunit Gpa1p identify a receptor subtype-biased mating defect. DeSimone, S.M., Kurjan, J. Mol. Gen. Genet. (1998) [Pubmed]
  18. Stoichiometry of G protein subunits affects the Saccharomyces cerevisiae mating pheromone signal transduction pathway. Cole, G.M., Stone, D.E., Reed, S.I. Mol. Cell. Biol. (1990) [Pubmed]
  19. Overexpression of the STE4 gene leads to mating response in haploid Saccharomyces cerevisiae. Whiteway, M., Hougan, L., Thomas, D.Y. Mol. Cell. Biol. (1990) [Pubmed]
  20. The Hog1 MAPK prevents cross talk between the HOG and pheromone response MAPK pathways in Saccharomyces cerevisiae. O'Rourke, S.M., Herskowitz, I. Genes Dev. (1998) [Pubmed]
  21. Interactions among the subunits of the G protein involved in Saccharomyces cerevisiae mating. Clark, K.L., Dignard, D., Thomas, D.Y., Whiteway, M. Mol. Cell. Biol. (1993) [Pubmed]
  22. Gbetagamma recruits Rho1 to the site of polarized growth during mating in budding yeast. Bar, E.E., Ellicott, A.T., Stone, D.E. J. Biol. Chem. (2003) [Pubmed]
  23. Substitutions in the pheromone-responsive Gbeta protein of Saccharomyces cerevisiae confer a defect in recovery from pheromone treatment. Li, E., Meldrum, E., Stratton, H.F., Stone, D.E. Genetics (1998) [Pubmed]
  24. Phosphorylation of the pheromone-responsive Gbeta protein of Saccharomyces cerevisiae does not affect its mating-specific signaling function. Li, E., Cismowski, M.J., Stone, D.E. Mol. Gen. Genet. (1998) [Pubmed]
  25. Sst2, a negative regulator of pheromone signaling in the yeast Saccharomyces cerevisiae: expression, localization, and genetic interaction and physical association with Gpa1 (the G-protein alpha subunit). Dohlman, H.G., Song, J., Ma, D., Courchesne, W.E., Thorner, J. Mol. Cell. Biol. (1996) [Pubmed]
WikiGenes - Universities