Functional Expression of Mammalian Receptors and G-Proteins in Yeast

  • K. J. Blumer
Part of the Handbook of Experimental Pharmacology book series (HEP, volume 108 / 2)


Biologists studying G-protein-linked signal transduction pathways have used heterologous expression systems to make many important discoveries, including the molecular description of pharmacologically distinct subtypes of receptors, and the specificity with which receptors, G-proteins, and their effectors interact with one another. However, commonly used expression systems, including those employing Xenopus oocytes or transfected mammalian cell lines, pose limitations for basic and applied scientists alike. Such systems are not usually amenable to rigorous formal genetic analysis of signal transduction pathways, and they are costly to use as biological screening tools in drug discovery programs.


Muscarinic Acetylcholine Receptor Pheromone Receptor Pheromone Response Mating Pheromone Ligand Binding Activity 
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  1. Anderson JA, Huprikar SS, Kochian LV, Lucas WJ, Gaber RF (1992) Functional expression of a probable Arabadopsis thaliana potassium channel in Saccharomyces cerevisiae. Proc Natl Acad Sci USA 89:3736–3740.PubMedCrossRefGoogle Scholar
  2. Andersson SGE, Kurland CG (1990) Codon preferences in free-living microorganisms. Microbiol Rev 54:198–210.PubMedGoogle Scholar
  3. Ballester R, Michaeli T, Ferguson K, Xu HP, McCormick F, Wigler M (1989) Genetic analysis of mammalian GAP expressed in yeast. Cell 594:681–686.CrossRefGoogle Scholar
  4. Blumer KJ, Reneke JE, Thorner J (1988) The STE2 gene product is the ligand binding component of the α-factor receptor of Saccharomyces cerevisiae. J Biol Chem 263:10836–10842.PubMedGoogle Scholar
  5. Blumer KJ, Thorner J (1991) Receptor-G protein signaling in yeast. Annu Rev Physiol 53:37–57.PubMedCrossRefGoogle Scholar
  6. Buckley NJ, Bonner TI, Buckley CM, Brann MR (1989) Antagonist binding proterties of five cloned muscarinic receptors expressed in CHO-K1 cells. Mol Pharm 35:469–476.Google Scholar
  7. Cartwright CP, Tipper DJ (1991) In vivo topological analysis of Ste2, a yeast plasma membrane protein, by using β-lactamase gene fusions. Mol Cell Biol 11:2620–2628.PubMedGoogle Scholar
  8. Cigan AM, Donahue TF (1987) Sequence and structural features associated with translational initiator regions in yeast — a review. Gene 59:1–18.PubMedCrossRefGoogle Scholar
  9. Dietzel C, Kurjan J (1987) The yeast SCG1 gene: a Gα-like protein implicated in the a-and α-factor response pathway. Cell 50:1001–1010.PubMedCrossRefGoogle Scholar
  10. Dohlman HG, Caron MG, DeBlasi A, Frielle T, Lefkowitz RJ (1990) Role of extracellular disulfide-bonded cysteines in the ligand binding function of the beta 2-adrenergic receptor. Biochemistry 29:2335–2342.PubMedCrossRefGoogle Scholar
  11. Freissmuth M, Casey PJ, Gilman AG (1989) G proteins control diverse pathways of transmembrane signalling. FASEB J 3:2125–2131.PubMedGoogle Scholar
  12. Gill G, Tjian R (1991) A highly conserved domain of TFIID displays species specificity in vivo. Cell: 65:333–340.PubMedCrossRefGoogle Scholar
  13. Huang H-J, Liao C-F, Yang B-C, Kuo T-T (1992) Functional expression of rat M5 muscarinic acetylcholine receptor in yeast. Biochem Biophys Res Comm 182:1180–1186.PubMedCrossRefGoogle Scholar
  14. Kang Y-S, Kane J, Kurjan J, Stadel JM, Tipper DJ (1990) Effects of expression of mammalian Gα and hybrid mammalian-yeast Gα proteins on the yeast pheromone response signal transduction pathway. Mol Cell Biol 10:2582–2590.PubMedGoogle Scholar
  15. King K, Dohlman HG, Thorner J, Caron MG, Lefkowitz RJ (1990) Control of yeast mating signal transduction by a mammalian β2-adrenergic receptor and Gs α subunit. Science 250:121–123.PubMedCrossRefGoogle Scholar
  16. LaMantia M, Miura T, Tachikawa H, Kaplan HA, Lennarz WJ, Mizunaga T (1991) Glycosylation site binding protein and protein disulfide isomerase are identical and essential for cell viability in yeast. Proc Natl Acad Sci USA 88:4453–4457.PubMedCrossRefGoogle Scholar
  17. Liao C-F, Themmen APN, Joho R, Barberis C, Birnbaumer M, Birnbaumer L (1989) Molecular cloning and expression of a fifth muscarinic acetylcholine receptor. J Biol Chem 264:7328–7337.PubMedGoogle Scholar
  18. Linder ME, Pang IH, Duronio RJ, Gordon JI, Sternweiss PC, Gilman AG (1991) Lipid modifications of G protein subunits. myristoylation of Go alpha increases its affinity for beta gamma. J Biol Chem 266:4654–4659.PubMedGoogle Scholar
  19. Marsh L, Neiman AM, Herskowitz I (1991) Signal transduction during pheromone response in yeast. Annu Rev Cell Biol 7:699–728.PubMedCrossRefGoogle Scholar
  20. Nakafuku M, Obara K, Kaibuchi K, Miyajima I, Miyajima A, Itoh H, Nakamura S, Arai K-I, Matsumoto K, Kaziro Y (1988) Isolation of a second yeast Saccharomyces cerevisiae gene (GPA2) coding for guanine nucleotide-binding regulatory protein: studies on its structure and possible functions. Proc Natl Acad Sci USA 85:1374–1378.PubMedCrossRefGoogle Scholar
  21. Payette P, Gossard F, Whiteway M, Dennis M (1990) Expression and pharmacological characterization of the human Ml muscarinic receptor in Saccharomyces cerevisiae. FEBS Lett 266:21–25.PubMedCrossRefGoogle Scholar
  22. Peralta EG, Ashkenazi A, Winslow JW, Smith DH, Ramachandran J, Capon DJ (1987) Distinct primary structures, ligand-binding properties and tissue-specific expression of four human muscarinic acetylcholine receptors. EMBO J 6:3923–3929.PubMedGoogle Scholar
  23. Raymond M, Gros P, Whiteway M, Thomas DJ (1992) Functional complementation of yeast ste6 by a mammalian multidrug resistance mdr gene. Science 256:232–234.PubMedCrossRefGoogle Scholar
  24. Rose MD, Misra L, Vogel JP (1989) KAR2, a karyogamy gene, is the yeast homolog of the mammalian BiP/GRP78 gene. Cell 48:1211–1221.CrossRefGoogle Scholar
  25. Sadler I, Chiang A, Kurihara T, Rothblatt J, Way J, Silver P (1989) A yeast gene important for protein assembly into the endoplasmic reticulum and the nucleus has homology to DnaJ, an Escherichia coli heat shock protein. J Cell Biol 109:2665–2675.PubMedCrossRefGoogle Scholar
  26. Schena M, Yamamoto KR (1989) Mammalian glucocortocoid receptor derivatives enhance transcription in yeast. Science 241:965–967.CrossRefGoogle Scholar
  27. Sentenac H, Bonneaud N, Minet M, Lacroute F, Salmon J-M, Gaymard F, Grignon C (1992) Cloning and expression in yeast of a plant potassium ion transport system. Science 256:663–665.PubMedCrossRefGoogle Scholar
  28. Singer SJ (1990) The structure and insertion of integral proteins in membranes. Annu Rev Cell Biol 6:247–296.PubMedCrossRefGoogle Scholar
  29. Stammes MA, Shieh BH, Chuman L, Harris GL, Zucker CS (1991) The cyclophilin homolog ninaA is a tissue-specific integral membrane protein required for the proper synthesis of a subset of drosophila rhodopsins. Cell 65:219–227.CrossRefGoogle Scholar
  30. Waldo GL, Northup JK, Perkins JP, Harden TK (1983) Characterization of an altered membrane form of the β-adrenergic receptor produced during agonist-induced desensitization. J Biol Chem 258:13900–13908.PubMedGoogle Scholar
  31. Xu GF, Lin B, Tanaka K, Dunn D, Wood D, Gesteland R, White R, Weiss R, Tamanoi F (1990) The catalytic domain of the neurofibromatosis type 1 gene product stimulates ras GTPase and complements ira mutants of S. cerevisiae. Cell 63:835–841.PubMedCrossRefGoogle Scholar
  32. Yellen G, Migeon JC (1990) Expression of Torpedo nicotinic acetylcholine receptor subunits in yeast is enhanced by use of yeast signal sequences. Gene 86:145–152.PubMedCrossRefGoogle Scholar

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© Springer-Verlag Berlin Heidelberg 1993

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  • K. J. Blumer

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