Abstract
In the yeast Saccharomyces cerevisiae, the activation of adenylate cyclase requires the products of the RAS genes and of CDC25. We isolated several dominant extragenic suppressors of the yeast cdc25 mutation. They did not suppress a thermosensitive allele of the adenylate cyclase gene (CDC35). One of these suppressors was a mutated RAS2 gene in which the transition C/G----T/A at position 455 resulted in replacement of threonine 152 by isoleucine in the protein. The same mutation in a v-Ha-ras gene reduces the affinity of p21 for guanine nucleotides (L.A. Feig, B. Pan, T.M. Roberts, and G.M. Cooper, Proc. Natl. Acad. Sci. USA 83:4607-4611, 1986). These results support a model in which the CDC25 gene product is the GDP-GTP exchange factor regulating the activity of the RAS gene product.
Full text
PDF



Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Baldari C., Cesareni G. Plasmids pEMBLY: new single-stranded shuttle vectors for the recovery and analysis of yeast DNA sequences. Gene. 1985;35(1-2):27–32. doi: 10.1016/0378-1119(85)90154-4. [DOI] [PubMed] [Google Scholar]
- Barbacid M. ras genes. Annu Rev Biochem. 1987;56:779–827. doi: 10.1146/annurev.bi.56.070187.004023. [DOI] [PubMed] [Google Scholar]
- Boutelet F., Petitjean A., Hilger F. Yeast cdc35 mutants are defective in adenylate cyclase and are allelic with cyr1 mutants while CAS1, a new gene, is involved in the regulation of adenylate cyclase. EMBO J. 1985 Oct;4(10):2635–2641. doi: 10.1002/j.1460-2075.1985.tb03981.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Boy-Marcotte E., Garreau H., Jacquet M. Cyclic AMP controls the switch between division cycle and resting state programs in response to ammonium availability in Saccharomyces cerevisiae. Yeast. 1987 Jun;3(2):85–93. doi: 10.1002/yea.320030205. [DOI] [PubMed] [Google Scholar]
- Broek D., Samiy N., Fasano O., Fujiyama A., Tamanoi F., Northup J., Wigler M. Differential activation of yeast adenylate cyclase by wild-type and mutant RAS proteins. Cell. 1985 Jul;41(3):763–769. doi: 10.1016/s0092-8674(85)80057-x. [DOI] [PubMed] [Google Scholar]
- Broek D., Toda T., Michaeli T., Levin L., Birchmeier C., Zoller M., Powers S., Wigler M. The S. cerevisiae CDC25 gene product regulates the RAS/adenylate cyclase pathway. Cell. 1987 Mar 13;48(5):789–799. doi: 10.1016/0092-8674(87)90076-6. [DOI] [PubMed] [Google Scholar]
- Camonis J. H., Kalékine M., Gondré B., Garreau H., Boy-Marcotte E., Jacquet M. Characterization, cloning and sequence analysis of the CDC25 gene which controls the cyclic AMP level of Saccharomyces cerevisiae. EMBO J. 1986 Feb;5(2):375–380. doi: 10.1002/j.1460-2075.1986.tb04222.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cannon J. F., Gibbs J. B., Tatchell K. Suppressors of the ras2 mutation of Saccharomyces cerevisiae. Genetics. 1986 Jun;113(2):247–264. doi: 10.1093/genetics/113.2.247. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Cannon J. F., Tatchell K. Characterization of Saccharomyces cerevisiae genes encoding subunits of cyclic AMP-dependent protein kinase. Mol Cell Biol. 1987 Aug;7(8):2653–2663. doi: 10.1128/mcb.7.8.2653. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dale R. M., McClure B. A., Houchins J. P. A rapid single-stranded cloning strategy for producing a sequential series of overlapping clones for use in DNA sequencing: application to sequencing the corn mitochondrial 18 S rDNA. Plasmid. 1985 Jan;13(1):31–40. doi: 10.1016/0147-619x(85)90053-8. [DOI] [PubMed] [Google Scholar]
- De Vendittis E., Vitelli A., Zahn R., Fasano O. Suppression of defective RAS1 and RAS2 functions in yeast by an adenylate cyclase activated by a single amino acid change. EMBO J. 1986 Dec 20;5(13):3657–3663. doi: 10.1002/j.1460-2075.1986.tb04696.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Dhar R., Nieto A., Koller R., DeFeo-Jones D., Scolnick E. M. Nucleotide sequence of two rasH related-genes isolated from the yeast Saccharomyces cerevisiae. Nucleic Acids Res. 1984 Apr 25;12(8):3611–3618. doi: 10.1093/nar/12.8.3611. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Feig L. A., Pan B. T., Roberts T. M., Cooper G. M. Isolation of ras GTP-binding mutants using an in situ colony-binding assay. Proc Natl Acad Sci U S A. 1986 Jul;83(13):4607–4611. doi: 10.1073/pnas.83.13.4607. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Goodrich G. A., Burrell H. R. Micromeasurement of nucleoside 5'-triphosphates using coupled bioluminescence. Anal Biochem. 1982 Dec;127(2):395–401. doi: 10.1016/0003-2697(82)90193-2. [DOI] [PubMed] [Google Scholar]
- Hinnen A., Hicks J. B., Fink G. R. Transformation of yeast. Proc Natl Acad Sci U S A. 1978 Apr;75(4):1929–1933. doi: 10.1073/pnas.75.4.1929. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jacquet M., Boy-Marcotte E., Rossier C., Kessin R. H. A fragment of Dictyostelium discoideum genomic DNA that complements the URA1 mutation of Saccharomyces cerivisiae. J Mol Appl Genet. 1982;1(6):513–525. [PubMed] [Google Scholar]
- Jurnak F. Structure of the GDP domain of EF-Tu and location of the amino acids homologous to ras oncogene proteins. Science. 1985 Oct 4;230(4721):32–36. doi: 10.1126/science.3898365. [DOI] [PubMed] [Google Scholar]
- Marshall M. S., Gibbs J. B., Scolnick E. M., Sigal I. S. Regulatory function of the Saccharomyces cerevisiae RAS C-terminus. Mol Cell Biol. 1987 Jul;7(7):2309–2315. doi: 10.1128/mcb.7.7.2309. [DOI] [PMC free article] [PubMed] [Google Scholar]
- McCormick F., Clark B. F., la Cour T. F., Kjeldgaard M., Norskov-Lauritsen L., Nyborg J. A model for the tertiary structure of p21, the product of the ras oncogene. Science. 1985 Oct 4;230(4721):78–82. doi: 10.1126/science.3898366. [DOI] [PubMed] [Google Scholar]
- Parent S. A., Fenimore C. M., Bostian K. A. Vector systems for the expression, analysis and cloning of DNA sequences in S. cerevisiae. Yeast. 1985 Dec;1(2):83–138. doi: 10.1002/yea.320010202. [DOI] [PubMed] [Google Scholar]
- Powers S., Kataoka T., Fasano O., Goldfarb M., Strathern J., Broach J., Wigler M. Genes in S. cerevisiae encoding proteins with domains homologous to the mammalian ras proteins. Cell. 1984 Mar;36(3):607–612. doi: 10.1016/0092-8674(84)90340-4. [DOI] [PubMed] [Google Scholar]
- Reynolds S. H., Stowers S. J., Patterson R. M., Maronpot R. R., Aaronson S. A., Anderson M. W. Activated oncogenes in B6C3F1 mouse liver tumors: implications for risk assessment. Science. 1987 Sep 11;237(4820):1309–1316. doi: 10.1126/science.3629242. [DOI] [PubMed] [Google Scholar]
- Robinson L. C., Gibbs J. B., Marshall M. S., Sigal I. S., Tatchell K. CDC25: a component of the RAS-adenylate cyclase pathway in Saccharomyces cerevisiae. Science. 1987 Mar 6;235(4793):1218–1221. doi: 10.1126/science.3547648. [DOI] [PubMed] [Google Scholar]
- Sanger F., Nicklen S., Coulson A. R. DNA sequencing with chain-terminating inhibitors. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5463–5467. doi: 10.1073/pnas.74.12.5463. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sigal I. S., Gibbs J. B., D'Alonzo J. S., Temeles G. L., Wolanski B. S., Socher S. H., Scolnick E. M. Mutant ras-encoded proteins with altered nucleotide binding exert dominant biological effects. Proc Natl Acad Sci U S A. 1986 Feb;83(4):952–956. doi: 10.1073/pnas.83.4.952. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Toda T., Cameron S., Sass P., Zoller M., Wigler M. Three different genes in S. cerevisiae encode the catalytic subunits of the cAMP-dependent protein kinase. Cell. 1987 Jul 17;50(2):277–287. doi: 10.1016/0092-8674(87)90223-6. [DOI] [PubMed] [Google Scholar]
- Tschumper G., Carbon J. Sequence of a yeast DNA fragment containing a chromosomal replicator and the TRP1 gene. Gene. 1980 Jul;10(2):157–166. doi: 10.1016/0378-1119(80)90133-x. [DOI] [PubMed] [Google Scholar]
- Walter M., Clark S. G., Levinson A. D. The oncogenic activation of human p21ras by a novel mechanism. Science. 1986 Aug 8;233(4764):649–652. doi: 10.1126/science.3487832. [DOI] [PubMed] [Google Scholar]