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Science 13 July 1990:
Vol. 249. no. 4965, pp. 165 - 169
DOI: 10.1126/science.1695391
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Articles

Science, Vol 249, Issue 4965, 165-169
Copyright © 1990 by American Association for the Advancement of Science

articles

Common modifications of trimeric G proteins and ras protein: involvement of polyisoprenylation

AA Finegold, WR Schafer, J Rine, M Whiteway, and F Tamanoi

Department of Biochemistry and Molecular Biology, University of Chicago, IL 60637.

The heterotrimeric guanine nucleotide-binding regulatory proteins act at the inner surface of the plasma membrane to relay information from cell surface receptors to effectors inside the cell. These G proteins are not integral membrane proteins, yet are membrane associated. The processing and function of the gamma subunit of the yeast G protein involved in mating-pheromone signal transduction was found to be affected by the same mutations that block ras processing. The nature of these mutations implied that the gamma subunit was polyisoprenylated and that this modification was necessary for membrane association and biological activity. A microbial screen was developed for pharmacological agents that inhibit polyisoprenylation and that have potential application in cancer therapy.


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
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A Kelch {beta} Propeller Featuring as a G{beta} Structural Mimic: Reinventing the Wheel?.
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A Selective Transport Route from Golgi to Late Endosomes that Requires the Yeast GGA Proteins.
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J. Cell Biol. 151, 587-600
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Prenylation of the Floral Transcription Factor APETALA1 Modulates Its Function.
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The Saccharomyces cerevisiae Rheb G-protein Is Involved in Regulating Canavanine Resistance and Arginine Uptake.
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Dual Lipid Modification Motifs in Galpha and Ggamma Subunits Are Required for Full Activity of the Pheromone Response Pathway in Saccharomyces cerevisiae.
C. L. Manahan, M. Patnana, K. J. Blumer, and M. E. Linder (2000)
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Dual Lipid Modification of the Yeast Ggamma Subunit Ste18p Determines Membrane Localization of Gbeta gamma.
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Mol. Cell. Biol. 19, 7705-7711
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Comprehensive evaluation of isoprenoid biosynthesis regulation in Saccharomyces cerevisiae utilizing the Genome Reporter Matrix(TM).
D. Dimster-Denk, J. Rine, J. Phillips, S. Scherer, P. Cundiff, K. DeBord, D. Gilliland, S. Hickman, A. Jarvis, L. Tong, et al. (1999)
J. Lipid Res. 40, 850-860
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Plasma membrane localization is required for RGS4 function in Saccharomyces cerevisiae.
S. P. Srinivasa, L. S. Bernstein, K. J. Blumer, and M. E. Linder (1998)
PNAS 95, 5584-5589
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Substrate specificity determinants in the farnesyltransferase beta -subunit.
C. E. Trueblood, V. L. Boyartchuk, and J. Rine (1997)
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Lovastatin Induces Apoptosis in Malignant Mesothelioma Cells.
J. B. RUBINS, T. GREATENS, R. A. KRATZKE, A. T. TAN, V. A. POLUNOVSKY, and P. BITTERMAN (1997)
Am. J. Respir. Crit. Care Med. 157, 1616-1622
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The Gbeta gamma Complex of the Yeast Pheromone Response Pathway. SUBCELLULAR FRACTIONATION AND PROTEIN-PROTEIN INTERACTIONS.
J. E. Hirschman, G. S. De Zutter, W. F. Simonds, and D. D. Jenness (1997)
J. Biol. Chem. 272, 240-248
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Photoreactive Analogues of Prenyl Diphosphates as Inhibitors and Probes of Human Protein Farnesyltransferase and Geranylgeranyltransferase Type I.
Y. E. Bukhtiyarov, C. A. Omer, and C. M. Allen (1995)
J. Biol. Chem. 270, 19035-19040
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Molecular Characterization of Ste20p, a Potential Mitogen-activated Protein or Extracellular Signal-regulated Kinase Kinase (MEK) Kinase Kinase from Saccharomycescerevisiae.
C. Wu, M. Whiteway, D. Y. Thomas, and E. Leberer (1995)
J. Biol. Chem. 270, 15984-15992
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Enzymatic coupling of cholesterol intermediates to a mating pheromone precursor and to the ras protein.
W. Schafer, C. Trueblood, C. Yang, M. Mayer, S Rosenberg, C. Poulter, S. Kim, and J Rine (1990)
Science 249, 1133-1139
   Abstract »    PDF »


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