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. 1986 Nov;5(11):2963–2971. doi: 10.1002/j.1460-2075.1986.tb04593.x

Involvement of ras in sexual differentiation but not in growth control in fission yeast

S A Nadin-Davis 1, A Nasim 1, D Beach 1
PMCID: PMC1167248  PMID: 16453723

Abstract

The function of the ras+ gene of Schizosaccharomyces pombe has been studied by constructing null and activated alleles of this gene. An activated allele (rasVal 12) inhibits conjugation but has no effect on cell growth, entry into stationary phase or sporulation. The phenotype of rasVal 12 is distinct from that caused by elevating the intracellular level of cAMP. This supports the hypothesis that ras of fission yeast does not modulate adenylate cyclase in a manner analogous to S. cerevisiae RAS. Introduction of a human ras sequence into fission yeast cells containing a non-functional null allele of ras restored the sexual differentiation process thus indicating that the human sequence can complement S. pombe ras. Our data suggest that although ras genes are highly conserved across a considerable evolutionary divide, the cellular function of the ras gene product varies in different organisms.

Keywords: differentiation, fission yeast, growth, ras

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Selected References

These references are in PubMed. This may not be the complete list of references from this article.

  1. Bar-Sagi D., Feramisco J. R. Microinjection of the ras oncogene protein into PC12 cells induces morphological differentiation. Cell. 1985 Oct;42(3):841–848. doi: 10.1016/0092-8674(85)90280-6. [DOI] [PubMed] [Google Scholar]
  2. Beach D., Piper M., Nurse P. Construction of a Schizosaccharomyces pombe gene bank in a yeast bacterial shuttle vector and its use to isolate genes by complementation. Mol Gen Genet. 1982;187(2):326–329. doi: 10.1007/BF00331138. [DOI] [PubMed] [Google Scholar]
  3. Beach D., Rodgers L., Gould J. ran1+ controls the transition from mitotic division to meiosis in fission yeast. Curr Genet. 1985;10(4):297–311. doi: 10.1007/BF00365626. [DOI] [PubMed] [Google Scholar]
  4. Beach D. Sexual differentiation is controlled by a protein kinase encoded by the ran1+ gene in fission yeast. Cold Spring Harb Symp Quant Biol. 1985;50:635–641. doi: 10.1101/sqb.1985.050.01.077. [DOI] [PubMed] [Google Scholar]
  5. Beckner S. K., Hattori S., Shih T. Y. The ras oncogene product p21 is not a regulatory component of adenylate cyclase. Nature. 1985 Sep 5;317(6032):71–72. doi: 10.1038/317071a0. [DOI] [PubMed] [Google Scholar]
  6. Birchmeier C., Broek D., Wigler M. ras proteins can induce meiosis in Xenopus oocytes. Cell. 1985 Dec;43(3 Pt 2):615–621. doi: 10.1016/0092-8674(85)90233-8. [DOI] [PubMed] [Google Scholar]
  7. 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]
  8. Capon D. J., Chen E. Y., Levinson A. D., Seeburg P. H., Goeddel D. V. Complete nucleotide sequences of the T24 human bladder carcinoma oncogene and its normal homologue. Nature. 1983 Mar 3;302(5903):33–37. doi: 10.1038/302033a0. [DOI] [PubMed] [Google Scholar]
  9. Chang E. H., Gonda M. A., Ellis R. W., Scolnick E. M., Lowy D. R. Human genome contains four genes homologous to transforming genes of Harvey and Kirsten murine sarcoma viruses. Proc Natl Acad Sci U S A. 1982 Aug;79(16):4848–4852. doi: 10.1073/pnas.79.16.4848. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Coffin J. M., Varmus H. E., Bishop J. M., Essex M., Hardy W. D., Jr, Martin G. S., Rosenberg N. E., Scolnick E. M., Weinberg R. A., Vogt P. K. Proposal for naming host cell-derived inserts in retrovirus genomes. J Virol. 1981 Dec;40(3):953–957. doi: 10.1128/jvi.40.3.953-957.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  11. DeFeo-Jones D., Scolnick E. M., Koller R., Dhar R. ras-Related gene sequences identified and isolated from Saccharomyces cerevisiae. Nature. 1983 Dec 15;306(5944):707–709. doi: 10.1038/306707a0. [DOI] [PubMed] [Google Scholar]
  12. DeFeo-Jones D., Tatchell K., Robinson L. C., Sigal I. S., Vass W. C., Lowy D. R., Scolnick E. M. Mammalian and yeast ras gene products: biological function in their heterologous systems. Science. 1985 Apr 12;228(4696):179–184. doi: 10.1126/science.3883495. [DOI] [PubMed] [Google Scholar]
  13. DeFeo D., Gonda M. A., Young H. A., Chang E. H., Lowy D. R., Scolnick E. M., Ellis R. W. Analysis of two divergent rat genomic clones homologous to the transforming gene of Harvey murine sarcoma virus. Proc Natl Acad Sci U S A. 1981 Jun;78(6):3328–3332. doi: 10.1073/pnas.78.6.3328. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Dhar R., Ellis R. W., Shih T. Y., Oroszlan S., Shapiro B., Maizel J., Lowy D., Scolnick E. Nucleotide sequence of the p21 transforming protein of Harvey murine sarcoma virus. Science. 1982 Sep 3;217(4563):934–936. doi: 10.1126/science.6287572. [DOI] [PubMed] [Google Scholar]
  15. 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]
  16. Ellis R. W., Defeo D., Shih T. Y., Gonda M. A., Young H. A., Tsuchida N., Lowy D. R., Scolnick E. M. The p21 src genes of Harvey and Kirsten sarcoma viruses originate from divergent members of a family of normal vertebrate genes. Nature. 1981 Aug 6;292(5823):506–511. doi: 10.1038/292506a0. [DOI] [PubMed] [Google Scholar]
  17. Fasano O., Taparowsky E., Fiddes J., Wigler M., Goldfarb M. Sequence and structure of the coding region of the human H-ras-1 gene from T24 bladder carcinoma cells. J Mol Appl Genet. 1983;2(2):173–180. [PubMed] [Google Scholar]
  18. Feramisco J. R., Gross M., Kamata T., Rosenberg M., Sweet R. W. Microinjection of the oncogene form of the human H-ras (T-24) protein results in rapid proliferation of quiescent cells. Cell. 1984 Aug;38(1):109–117. doi: 10.1016/0092-8674(84)90531-2. [DOI] [PubMed] [Google Scholar]
  19. Finkel T., Der C. J., Cooper G. M. Activation of ras genes in human tumors does not affect localization, modification, or nucleotide binding properties of p21. Cell. 1984 May;37(1):151–158. doi: 10.1016/0092-8674(84)90310-6. [DOI] [PubMed] [Google Scholar]
  20. Fukui Y., Kaziro Y. Molecular cloning and sequence analysis of a ras gene from Schizosaccharomyces pombe. EMBO J. 1985 Mar;4(3):687–691. doi: 10.1002/j.1460-2075.1985.tb03684.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Fukui Y., Kozasa T., Kaziro Y., Takeda T., Yamamoto M. Role of a ras homolog in the life cycle of Schizosaccharomyces pombe. Cell. 1986 Jan 31;44(2):329–336. doi: 10.1016/0092-8674(86)90767-1. [DOI] [PubMed] [Google Scholar]
  22. Hurley J. B., Simon M. I., Teplow D. B., Robishaw J. D., Gilman A. G. Homologies between signal transducing G proteins and ras gene products. Science. 1984 Nov 16;226(4676):860–862. doi: 10.1126/science.6436980. [DOI] [PubMed] [Google Scholar]
  23. Kamata T., Feramisco J. R. Epidermal growth factor stimulates guanine nucleotide binding activity and phosphorylation of ras oncogene proteins. Nature. 1984 Jul 12;310(5973):147–150. doi: 10.1038/310147a0. [DOI] [PubMed] [Google Scholar]
  24. Kataoka T., Broek D., Wigler M. DNA sequence and characterization of the S. cerevisiae gene encoding adenylate cyclase. Cell. 1985 Dec;43(2 Pt 1):493–505. doi: 10.1016/0092-8674(85)90179-5. [DOI] [PubMed] [Google Scholar]
  25. Kataoka T., Powers S., Cameron S., Fasano O., Goldfarb M., Broach J., Wigler M. Functional homology of mammalian and yeast RAS genes. Cell. 1985 Jan;40(1):19–26. doi: 10.1016/0092-8674(85)90304-6. [DOI] [PubMed] [Google Scholar]
  26. Kataoka T., Powers S., McGill C., Fasano O., Strathern J., Broach J., Wigler M. Genetic analysis of yeast RAS1 and RAS2 genes. Cell. 1984 Jun;37(2):437–445. doi: 10.1016/0092-8674(84)90374-x. [DOI] [PubMed] [Google Scholar]
  27. Lochrie M. A., Hurley J. B., Simon M. I. Sequence of the alpha subunit of photoreceptor G protein: homologies between transducin, ras, and elongation factors. Science. 1985 Apr 5;228(4695):96–99. doi: 10.1126/science.3856323. [DOI] [PubMed] [Google Scholar]
  28. Losson R., Lacroute F. Plasmids carrying the yeast OMP decarboxylase structural and regulatory genes: transcription regulation in a foreign environment. Cell. 1983 Feb;32(2):371–377. doi: 10.1016/0092-8674(83)90456-7. [DOI] [PubMed] [Google Scholar]
  29. 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]
  30. McGrath J. P., Capon D. J., Goeddel D. V., Levinson A. D. Comparative biochemical properties of normal and activated human ras p21 protein. Nature. 1984 Aug 23;310(5979):644–649. doi: 10.1038/310644a0. [DOI] [PubMed] [Google Scholar]
  31. Nadin-Davis S. A., Yang R. C., Narang S. A., Nasim A. The cloning and characterization of a RAS gene from Schizosaccharomyces pombe. J Mol Evol. 1986;23(1):41–51. doi: 10.1007/BF02100997. [DOI] [PubMed] [Google Scholar]
  32. Neuman-Silberberg F. S., Schejter E., Hoffmann F. M., Shilo B. Z. The Drosophila ras oncogenes: structure and nucleotide sequence. Cell. 1984 Jul;37(3):1027–1033. doi: 10.1016/0092-8674(84)90437-9. [DOI] [PubMed] [Google Scholar]
  33. Norrander J., Kempe T., Messing J. Construction of improved M13 vectors using oligodeoxynucleotide-directed mutagenesis. Gene. 1983 Dec;26(1):101–106. doi: 10.1016/0378-1119(83)90040-9. [DOI] [PubMed] [Google Scholar]
  34. 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]
  35. Reddy E. P., Reynolds R. K., Santos E., Barbacid M. A point mutation is responsible for the acquisition of transforming properties by the T24 human bladder carcinoma oncogene. Nature. 1982 Nov 11;300(5888):149–152. doi: 10.1038/300149a0. [DOI] [PubMed] [Google Scholar]
  36. Reymond C. D., Gomer R. H., Mehdy M. C., Firtel R. A. Developmental regulation of a Dictyostelium gene encoding a protein homologous to mammalian ras protein. Cell. 1984 Nov;39(1):141–148. doi: 10.1016/0092-8674(84)90199-5. [DOI] [PubMed] [Google Scholar]
  37. Russell P., Nurse P. cdc25+ functions as an inducer in the mitotic control of fission yeast. Cell. 1986 Apr 11;45(1):145–153. doi: 10.1016/0092-8674(86)90546-5. [DOI] [PubMed] [Google Scholar]
  38. Sadler S. E., Schechter A. L., Tabin C. J., Maller J. L. Antibodies to the ras gene product inhibit adenylate cyclase and accelerate progesterone-induced cell division in Xenopus laevis oocytes. Mol Cell Biol. 1986 Feb;6(2):719–722. doi: 10.1128/mcb.6.2.719. [DOI] [PMC free article] [PubMed] [Google Scholar]
  39. 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]
  40. Scher C. D., Scolnick E. M., Siegler R. Induction of erythroid leukaemia by Harvey and Kirsten sarcoma viruses. Nature. 1975 Jul 17;256(5514):225–226. doi: 10.1038/256225a0. [DOI] [PubMed] [Google Scholar]
  41. Scolnick E. M., Papageorge A. G., Shih T. Y. Guanine nucleotide-binding activity as an assay for src protein of rat-derived murine sarcoma viruses. Proc Natl Acad Sci U S A. 1979 Oct;76(10):5355–5359. doi: 10.1073/pnas.76.10.5355. [DOI] [PMC free article] [PubMed] [Google Scholar]
  42. Shih T. Y., Weeks M. O., Young H. A., Scholnick E. M. Identification of a sarcoma virus-coded phosphoprotein in nonproducer cells transformed by Kirsten or Harvey murine sarcoma virus. Virology. 1979 Jul 15;96(1):64–79. doi: 10.1016/0042-6822(79)90173-9. [DOI] [PubMed] [Google Scholar]
  43. Sweet R. W., Yokoyama S., Kamata T., Feramisco J. R., Rosenberg M., Gross M. The product of ras is a GTPase and the T24 oncogenic mutant is deficient in this activity. Nature. 1984 Sep 20;311(5983):273–275. doi: 10.1038/311273a0. [DOI] [PubMed] [Google Scholar]
  44. Tabin C. J., Bradley S. M., Bargmann C. I., Weinberg R. A., Papageorge A. G., Scolnick E. M., Dhar R., Lowy D. R., Chang E. H. Mechanism of activation of a human oncogene. Nature. 1982 Nov 11;300(5888):143–149. doi: 10.1038/300143a0. [DOI] [PubMed] [Google Scholar]
  45. Tamanoi F., Walsh M., Kataoka T., Wigler M. A product of yeast RAS2 gene is a guanine nucleotide binding protein. Proc Natl Acad Sci U S A. 1984 Nov;81(22):6924–6928. doi: 10.1073/pnas.81.22.6924. [DOI] [PMC free article] [PubMed] [Google Scholar]
  46. Taparowsky E., Suard Y., Fasano O., Shimizu K., Goldfarb M., Wigler M. Activation of the T24 bladder carcinoma transforming gene is linked to a single amino acid change. Nature. 1982 Dec 23;300(5894):762–765. doi: 10.1038/300762a0. [DOI] [PubMed] [Google Scholar]
  47. Tatchell K., Robinson L. C., Breitenbach M. RAS2 of Saccharomyces cerevisiae is required for gluconeogenic growth and proper response to nutrient limitation. Proc Natl Acad Sci U S A. 1985 Jun;82(11):3785–3789. doi: 10.1073/pnas.82.11.3785. [DOI] [PMC free article] [PubMed] [Google Scholar]
  48. Temeles G. L., Gibbs J. B., D'Alonzo J. S., Sigal I. S., Scolnick E. M. Yeast and mammalian ras proteins have conserved biochemical properties. Nature. 1985 Feb 21;313(6004):700–703. doi: 10.1038/313700a0. [DOI] [PubMed] [Google Scholar]
  49. Toda T., Uno I., Ishikawa T., Powers S., Kataoka T., Broek D., Cameron S., Broach J., Matsumoto K., Wigler M. In yeast, RAS proteins are controlling elements of adenylate cyclase. Cell. 1985 Jan;40(1):27–36. doi: 10.1016/0092-8674(85)90305-8. [DOI] [PubMed] [Google Scholar]
  50. Yanisch-Perron C., Vieira J., Messing J. Improved M13 phage cloning vectors and host strains: nucleotide sequences of the M13mp18 and pUC19 vectors. Gene. 1985;33(1):103–119. doi: 10.1016/0378-1119(85)90120-9. [DOI] [PubMed] [Google Scholar]
  51. Zoller M. J., Smith M. Oligonucleotide-directed mutagenesis of DNA fragments cloned into M13 vectors. Methods Enzymol. 1983;100:468–500. doi: 10.1016/0076-6879(83)00074-9. [DOI] [PubMed] [Google Scholar]

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