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Gene Review

STE5  -  Ste5p

Saccharomyces cerevisiae S288c

Synonyms: HMD3, NUL3, Protein STE5, YD8557.12, YDR103W
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Disease relevance of STE5


High impact information on STE5

  • Analysis of double mutants suggests that the STE4 gene product functions after the SCG1 product but before the STE5 product [2].
  • Unlike wild-type Ste5, the mutant did not appear to oligomerize; however, when fused to a heterologous dimerization domain (glutathione S-transferase), the chimeric protein restored mating in an ste5Delta cell and an ste4Delta ste5Delta double mutant [3].
  • 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 [3].
  • An amino-terminal fragment of the MAP kinase scaffold protein Ste5p that interfered with pheromone-induced cell cycle arrest was identified [4].
  • Altering residues (R407S K411S) equivalent to those that mediate phosphoinositide binding in other PH domains abolishes Ste5 function [5].

Biological context of STE5


Anatomical context of STE5

  • Ste5p remains stably bound at the plasma membrane, unlike activated Fus3p, which dissociates from Ste5p and translocates to the nucleus [10].
  • Once Ste11 is activated, signaling through the mating pathway remains minimal but is substantially amplified when Ste5 is recruited to the membrane either by the Gbetagamma dimer or by direct membrane targeting, even to internal membranes [11].
  • Indeed, in both yrb1ts mutants, Ste5 (scaffold protein for the pheromone response MAPK cascade) is mislocalized to the cytosol, even in the absence of pheromone [12].

Associations of STE5 with chemical compounds

  • Overexpression of Ste5p under galactose control activated the pheromone response pathway [13].
  • Here we demonstrate that Ste4 and Ste5 activate Kss1 during IG and in response to multiple stimuli including butanol [14].

Physical interactions of STE5

  • Measurement of relative binding affinities showed that the STE11 protein tightly interacts with the STE5 protein for its stabilization [15].
  • In cells with a constitutively activated pheromone response pathway, epitope-tagged Ste4p was coimmunoprecipitated with Ste5p [4].
  • Differences in the ability of constitutive Ste7 variants to bind the MAPKs and Ste5 account for the selective activation of Kss1 [16].

Enzymatic interactions of STE5

  • Fourth Ste5 is phosphorylated by Fus3 in purified complexes and copurifies with an additional protein kinase(s) [17].
  • During vegetative growth, Ste5p is basally phosphorylated through a process regulated by the CDK Cdc28p [18].

Regulatory relationships of STE5

  • The mating defects of the ste2 deletion mutant and the temperature-sensitive ste4-3 mutant were also suppressed by overexpression of wild-type STE5 [6].
  • These observations suggest the possibility that Ste5 promotes signal transduction by tethering Fus3 to its activating protein kinase(s) [17].
  • Cdc24 regulates nuclear shuttling and recruitment of the Ste5 scaffold to a heterotrimeric G protein in Saccharomyces cerevisiae [19].
  • Ste5 activates Kss1 by generating a pool of active MAPKKK (Ste11), whereas additional scaffolding is needed to activate Fus3 [14].

Other interactions of STE5

  • 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].
  • Defects at one step (requiring the STE2 gene are suppressed (directly or indirectly) by mutation sst2-1, whereas defects at the other step (requiring the STE5 gene) are suppressed by the ros1-1 mutation [21].
  • Genetic relationships between the G protein beta gamma complex, Ste5p, Ste20p and Cdc42p: investigation of effector roles in the yeast pheromone response pathway [13].
  • We provide genetic evidence for a functional interrelationship between the STE5 gene product and the Ste20 protein kinase [9].
  • Second, Ste5 associates with Fus3 in vivo as demonstrated by the two-hybrid system and by two methods of copurification [17].

Analytical, diagnostic and therapeutic context of STE5

  • Immunoblotting with anti-Ste5 antibodies indicated that the phenotype was not due to an increased level of the mutant STE5 protein [6].
  • Immunodetection and Northern blot analyses showed that the low level of the STE5 protein in the ste11 delta mutant is not due to the level of gene expression but to that of protein stability [15].
  • 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 [4].


  1. Mapping of a yeast G protein betagamma signaling interaction. Dowell, S.J., Bishop, A.L., Dyos, S.L., Brown, A.J., Whiteway, M.S. Genetics (1998) [Pubmed]
  2. Constitutive mutants in the yeast pheromone response: ordered function of the gene products. Blinder, D., Bouvier, S., Jenness, D.D. Cell (1989) [Pubmed]
  3. Ste5 RING-H2 domain: role in Ste4-promoted oligomerization for yeast pheromone signaling. Inouye, C., Dhillon, N., Thorner, J. Science (1997) [Pubmed]
  4. 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]
  5. Function of the MAPK scaffold protein, Ste5, requires a cryptic PH domain. Garrenton, L.S., Young, S.L., Thorner, J. Genes Dev. (2006) [Pubmed]
  6. 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]
  7. Function of the ste signal transduction pathway for mating pheromones sustains MAT alpha 1 transcription in Saccharomyces cerevisiae. Mukai, Y., Harashima, S., Oshima, Y. Mol. Cell. Biol. (1993) [Pubmed]
  8. Mutational analysis suggests that activation of the yeast pheromone response mitogen-activated protein kinase pathway involves conformational changes in the Ste5 scaffold protein. Sette, C., Inouye, C.J., Stroschein, S.L., Iaquinta, P.J., Thorner, J. Mol. Biol. Cell (2000) [Pubmed]
  9. Cloning of Saccharomyces cerevisiae STE5 as a suppressor of a Ste20 protein kinase mutant: structural and functional similarity of Ste5 to Far1. Leberer, E., Dignard, D., Harcus, D., Hougan, L., Whiteway, M., Thomas, D.Y. Mol. Gen. Genet. (1993) [Pubmed]
  10. MAP kinase dynamics in response to pheromones in budding yeast. van Drogen, F., Stucke, V.M., Jorritsma, G., Peter, M. Nat. Cell Biol. (2001) [Pubmed]
  11. Dual role for membrane localization in yeast MAP kinase cascade activation and its contribution to signaling fidelity. Lamson, R.E., Takahashi, S., Winters, M.J., Pryciak, P.M. Curr. Biol. (2006) [Pubmed]
  12. Mutations in the YRB1 gene encoding yeast ran-binding-protein-1 that impair nucleocytoplasmic transport and suppress yeast mating defects. Künzler, M., Trueheart, J., Sette, C., Hurt, E., Thorner, J. Genetics (2001) [Pubmed]
  13. 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]
  14. 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]
  15. Saccharomyces cerevisiae STE11 may contribute to the stabilities of a scaffold protein, STE5, in the pheromone signaling pathway. Kim, S.H., Lee, S.K., Choi, K.Y. Mol. Cells (1998) [Pubmed]
  16. Persistent activation by constitutive Ste7 promotes Kss1-mediated invasive growth but fails to support Fus3-dependent mating in yeast. Maleri, S., Ge, Q., Hackett, E.A., Wang, Y., Dohlman, H.G., Errede, B. Mol. Cell. Biol. (2004) [Pubmed]
  17. The MAP kinase Fus3 associates with and phosphorylates the upstream signaling component Ste5. Kranz, J.E., Satterberg, B., Elion, E.A. Genes Dev. (1994) [Pubmed]
  18. Localized feedback phosphorylation of Ste5p scaffold by associated MAPK cascade. Flotho, A., Simpson, D.M., Qi, M., Elion, E.A. J. Biol. Chem. (2004) [Pubmed]
  19. Cdc24 regulates nuclear shuttling and recruitment of the Ste5 scaffold to a heterotrimeric G protein in Saccharomyces cerevisiae. Wang, Y., Chen, W., Simpson, D.M., Elion, E.A. J. Biol. Chem. (2005) [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. 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]
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