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Gene Review

STE3  -  Ste3p

Saccharomyces cerevisiae S288c

Synonyms: Pheromone a factor receptor, YKL178C
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Disease relevance of STE3


High impact information on STE3

  • Control of yeast cell type by the mating type locus: positive regulation of the alpha-specific STE3 gene by the MAT alpha 1 product [3].
  • The STE3 gene was cloned by screening a yeast genomic clone bank for plasmids that complement the mating defect of ste3 mutants [3].
  • The yeast a-factor receptor (Ste3p) is subject to two mechanistically distinct modes of endocytosis: a constitutive, ligand-independent pathway and a ligand-dependent uptake pathway [4].
  • Together with sequences identified in two other yeast plasma membrane proteins, the STE3 sequence defines a new class of ubiquitination/endocytosis signal [5].
  • Moreover, endocytosis of Ste3p is dramatically decreased in yck(ts) cells and is partially restored by the AP suppressor mutations [6].

Biological context of STE3

  • Common signal transduction system shared by STE2 and STE3 in haploid cells of Saccharomyces cerevisiae: autocrine cell-cycle arrest results from forced expression of STE2 [7].
  • These results are consistent with the idea that STE2 encodes an alpha-factor receptor and STE3 encodes an a-factor receptor, and suggest that both alpha- and a-factors may generate an exchangeable signal(s) within haploid cells [7].
  • Analyses of these complexes by DNase I footprinting demonstrate that the PRTF binding site is confined to the palindromic P-box sequence in the case of the STE3 UAS, but extends symmetrically from this central region to cover 28 bp for the STE2 UAS [8].
  • The Saccharomyces cerevisiae a-factor receptor (STE3) is subject to two modes of endocytosis: a constitutive process that occurs in the absence of ligand and a regulated process that is triggered by binding of ligand [9].
  • Finally, the DNA sequence of STE3, which we report here, encodes a protein of 470 amino acid residues that contains seven distinct hydrophobic segments of sufficient length to span a lipid bilayer [10].

Anatomical context of STE3

  • Ste3p undergoes rapid, ligand-independent turnover that depends on vacuolar proteases and also on transport of the receptor from surface to vacuole (i.e., endocytosis) (Davis, N.G., J.L.Horecka, and G.F. Sprague, Jr., 1993 J. Cell Biol. 122:53-65) [11].
  • Despite the block to constitutive endocytosis exhibited by akr1 delta cells, they are competent to carry out ligand-mediated endocytosis of Ste3p [12].
  • These results suggest that assembly of vacuolar ATPase at the early endosome is required for transport of both Ste3p and Kex2p from the early endosome to the PVC and support a model in which cycling through the early endosome is part of the normal itinerary of Kex2p and other TGN-resident proteins [13].

Associations of STE3 with chemical compounds

  • Induction of STE3 RNA occurs even if protein synthesis is blocked by cycloheximide [14].
  • Dimethyl sulfate, DNase I and micrococcal nuclease DNA cleavage were combined with the ligation-mediated polymerase chain reaction to obtain high resolution maps of the promoter regions for two cell-type-specific genes: the a-specific STE2 gene and the alpha-specific STE3 gene [15].
  • The large clade includes the rhodopsin family (family A), the glucagon receptor family (family B), cyclic AMP receptors (family F), an Arabidopsis thaliana receptor, the Frizzled family and probably also the STE3 pheromone receptors (family E) and vomeronasal receptors type 1 [16].
  • In vitro assays demonstrated the ability of the receptors to promote mixing of proteoliposomes containing phosphatidylserine, potentially based on a pheromone-dependent interaction between Ste2p and Ste3p that was confirmed by tandem affinity purification and cellular pull-down assays [17].

Physical interactions of STE3

  • Vps9p ubiquitin binding is required for efficient endocytosis of Ste3p but not for the delivery of the biosynthetic cargo carboxypeptidase Y to the vacuole [18].

Regulatory relationships of STE3


Other interactions of STE3

  • Quantitative band shift electrophoresis was used to determine the equilibrium dissociation constants that describe the multicomponent binding equilibrium between the PRTF and MAT alpha 1 proteins, and alpha-specific STE3 upstream activating sequence (UAS) DNA [8].
  • In addition, transcripts of the MF alpha 1 and STE3 genes, which encode the alpha-factor precursor and the alpha-factor receptor, respectively, are greatly reduced in this mutant [22].
  • Moreover, in vps8 cells, there is defective down-regulation from the cell surface of the mating receptor Ste3, consistent with persistent receptor recycling from an endosomal compartment to the plasma membrane [23].
  • Surprisingly, the STE3 3' UT is not sufficient to accelerate the turnover of the stable PGK1 transcript unless portions of the PGK1 coding region are first deleted [24].
  • Homologous sequences with these elements were found in other alpha-specific genes, MF alpha 2 and STE3, and may mediate activation of this set of genes by MAT alpha 1 [25].


  1. 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]
  2. Lithium in the mating response and cell cycle of Saccharomyces cerevisiae. Smith, B.E., O'Day, D.H., Proteau, G.A. Biochem. Biophys. Res. Commun. (1995) [Pubmed]
  3. Control of yeast cell type by the mating type locus: positive regulation of the alpha-specific STE3 gene by the MAT alpha 1 product. Sprague, G.F., Jensen, R., Herskowitz, I. Cell (1983) [Pubmed]
  4. Recycling of the yeast a-factor receptor. Chen, L., Davis, N.G. J. Cell Biol. (2000) [Pubmed]
  5. A large PEST-like sequence directs the ubiquitination, endocytosis, and vacuolar degradation of the yeast a-factor receptor. Roth, A.F., Sullivan, D.M., Davis, N.G. J. Cell Biol. (1998) [Pubmed]
  6. Suppressors of YCK-encoded yeast casein kinase 1 deficiency define the four subunits of a novel clathrin AP-like complex. Panek, H.R., Stepp, J.D., Engle, H.M., Marks, K.M., Tan, P.K., Lemmon, S.K., Robinson, L.C. EMBO J. (1997) [Pubmed]
  7. Common signal transduction system shared by STE2 and STE3 in haploid cells of Saccharomyces cerevisiae: autocrine cell-cycle arrest results from forced expression of STE2. Nakayama, N., Miyajima, A., Arai, K. EMBO J. (1987) [Pubmed]
  8. Interactions of purified transcription factors: binding of yeast MAT alpha 1 and PRTF to cell type-specific, upstream activating sequences. Tan, S., Ammerer, G., Richmond, T.J. EMBO J. (1988) [Pubmed]
  9. Cis- and trans-acting functions required for endocytosis of the yeast pheromone receptors. Davis, N.G., Horecka, J.L., Sprague, G.F. J. Cell Biol. (1993) [Pubmed]
  10. Evidence the yeast STE3 gene encodes a receptor for the peptide pheromone a factor: gene sequence and implications for the structure of the presumed receptor. Hagen, D.C., McCaffrey, G., Sprague, G.F. Proc. Natl. Acad. Sci. U.S.A. (1986) [Pubmed]
  11. Ubiquitination of the yeast a-factor receptor. Roth, A.F., Davis, N.G. J. Cell Biol. (1996) [Pubmed]
  12. The ankyrin repeat-containing protein Akr1p is required for the endocytosis of yeast pheromone receptors. Givan, S.A., Sprague, G.F. Mol. Biol. Cell (1997) [Pubmed]
  13. Soi3p/Rav1p functions at the early endosome to regulate endocytic trafficking to the vacuole and localization of trans-Golgi network transmembrane proteins. Sipos, G., Brickner, J.H., Brace, E.J., Chen, L., Rambourg, A., Kepes, F., Fuller, R.S. Mol. Biol. Cell (2004) [Pubmed]
  14. Induction of the yeast alpha-specific STE3 gene by the peptide pheromone a-factor. Hagen, D.C., Sprague, G.F. J. Mol. Biol. (1984) [Pubmed]
  15. Genomic footprinting of the promoter regions of STE2 and STE3 genes in the yeast Saccharomyces cerevisiae. Ganter, B., Tan, S., Richmond, T.J. J. Mol. Biol. (1993) [Pubmed]
  16. Evidence for kinship between diverse G-protein coupled receptors. Josefsson, L.G. Gene (1999) [Pubmed]
  17. A role for a complex between activated G protein-coupled receptors in yeast cellular mating. Shi, C., Kaminskyj, S., Caldwell, S., Loewen, M.C. Proc. Natl. Acad. Sci. U.S.A. (2007) [Pubmed]
  18. Vps9p CUE domain ubiquitin binding is required for efficient endocytic protein traffic. Davies, B.A., Topp, J.D., Sfeir, A.J., Katzmann, D.J., Carney, D.S., Tall, G.G., Friedberg, A.S., Deng, L., Chen, Z., Horazdovsky, B.F. J. Biol. Chem. (2003) [Pubmed]
  19. Relative contributions of MCM1 and STE12 to transcriptional activation of a- and alpha-specific genes from Saccharomyces cerevisiae. Hwang-Shum, J.J., Hagen, D.C., Jarvis, E.E., Westby, C.A., Sprague, G.F. Mol. Gen. Genet. (1991) [Pubmed]
  20. Feedback phosphorylation of the yeast a-factor receptor requires activation of the downstream signaling pathway from G protein through mitogen-activated protein kinase. Feng, Y., Davis, N.G. Mol. Cell. Biol. (2000) [Pubmed]
  21. Ubiquitin-independent entry into the yeast recycling pathway. Chen, L., Davis, N.G. Traffic (2002) [Pubmed]
  22. Saccharomyces cerevisiae protein involved in plasmid maintenance is necessary for mating of MAT alpha cells. Passmore, S., Maine, G.T., Elble, R., Christ, C., Tye, B.K. J. Mol. Biol. (1988) [Pubmed]
  23. An endosome-to-plasma membrane pathway involved in trafficking of a mutant plasma membrane ATPase in yeast. Luo, W., Chang, A. Mol. Biol. Cell (2000) [Pubmed]
  24. Analysis of chimeric mRNAs derived from the STE3 mRNA identifies multiple regions within yeast mRNAs that modulate mRNA decay. Heaton, B., Decker, C., Muhlrad, D., Donahue, J., Jacobson, A., Parker, R. Nucleic Acids Res. (1992) [Pubmed]
  25. Identification of sequence elements that confer cell-type-specific control of MF alpha 1 expression in Saccharomyces cerevisiae. Inokuchi, K., Nakayama, A., Hishinuma, F. Mol. Cell. Biol. (1987) [Pubmed]
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