Skip to main content
Journal of Virology logoLink to Journal of Virology
. 1989 Feb;63(2):753–758. doi: 10.1128/jvi.63.2.753-758.1989

Polyomavirus transforms rat F111 and mouse NIH 3T3 cells by different mechanisms.

L Raptis 1, J B Bolen 1
PMCID: PMC247747  PMID: 2463382

Abstract

Polyomavirus middle tumor antigen (mT) was expressed in a line of mouse NIH 3T3 cells under control of the dexamethasone-regulatable mouse mammary tumor virus promotor. Contrary to rat F111 cells which were rendered anchorage independent by mT expression alone (L. Raptis, H. Lamfrom, and T.L. Benjamin, Mol. Cell. Biol. 5:2476-2487, 1985), mT-producing NIH 3T3 cells were unable to grow in agar even after full mT induction. The mT:pp60c-src-associated phosphatidylinositol kinase was activated in these cells to a degree similar to that in fully transformed cells expressing the small and large T antigens, in addition to mT. We therefore propose that the stimulation of this phosphatidylinositol kinase, although apparently necessary, is not sufficient for transformation of NIH 3T3 cells by polyomavirus.

Full text

PDF
753

Images in this article

Selected References

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

  1. Aharonov A., Pruss R. M., Herschman H. R. Epidermal growth factor. Relationship between receptor regulation and mitogenesis in 3T3 cells. J Biol Chem. 1978 Jun 10;253(11):3970–3977. [PubMed] [Google Scholar]
  2. Benjamin T. L. Host range mutants of polyoma virus. Proc Natl Acad Sci U S A. 1970 Sep;67(1):394–399. doi: 10.1073/pnas.67.1.394. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Blochlinger K., Diggelmann H. Hygromycin B phosphotransferase as a selectable marker for DNA transfer experiments with higher eucaryotic cells. Mol Cell Biol. 1984 Dec;4(12):2929–2931. doi: 10.1128/mcb.4.12.2929. [DOI] [PMC free article] [PubMed] [Google Scholar]
  4. Bolen J. B., DeSeau V., O'Shaughnessy J., Amini S. Analysis of middle tumor antigen and pp60c-src interactions in polyomavirus-transformed rat cells. J Virol. 1987 Oct;61(10):3299–3305. doi: 10.1128/jvi.61.10.3299-3305.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  5. Bolen J. B., Israel M. A. Middle tumor antigen of polyomavirus transformation-defective mutant NG59 is associated with pp60c-src. J Virol. 1985 Jan;53(1):114–119. doi: 10.1128/jvi.53.1.114-119.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Bolen J. B., Thiele C. J., Israel M. A., Yonemoto W., Lipsich L. A., Brugge J. S. Enhancement of cellular src gene product associated tyrosyl kinase activity following polyoma virus infection and transformation. Cell. 1984 Oct;38(3):767–777. doi: 10.1016/0092-8674(84)90272-1. [DOI] [PubMed] [Google Scholar]
  7. Carmichael G. G., Schaffhausen B. S., Dorsky D. I., Oliver D. B., Benjamin T. L. Carboxy terminus of polyoma middle-sized tumor antigen is required for attachment to membranes, associated protein kinase activities, and cell transformation. Proc Natl Acad Sci U S A. 1982 Jun;79(11):3579–3583. doi: 10.1073/pnas.79.11.3579. [DOI] [PMC free article] [PubMed] [Google Scholar]
  8. Cheng S. H., Markland W., Markham A. F., Smith A. E. Mutations around the NG59 lesion indicate an active association of polyoma virus middle-T antigen with pp60c-src is required for cell transformation. EMBO J. 1986 Feb;5(2):325–334. doi: 10.1002/j.1460-2075.1986.tb04216.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  9. Cherington V., Morgan B., Spiegelman B. M., Roberts T. M. Recombinant retroviruses that transduce individual polyoma tumor antigens: effects on growth and differentiation. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4307–4311. doi: 10.1073/pnas.83.12.4307. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Cooper J. A., Gould K. L., Cartwright C. A., Hunter T. Tyr527 is phosphorylated in pp60c-src: implications for regulation. Science. 1986 Mar 21;231(4744):1431–1434. doi: 10.1126/science.2420005. [DOI] [PubMed] [Google Scholar]
  11. Cooper J. A., King C. S. Dephosphorylation or antibody binding to the carboxy terminus stimulates pp60c-src. Mol Cell Biol. 1986 Dec;6(12):4467–4477. doi: 10.1128/mcb.6.12.4467. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Courtneidge S. A. Activation of the pp60c-src kinase by middle T antigen binding or by dephosphorylation. EMBO J. 1985 Jun;4(6):1471–1477. doi: 10.1002/j.1460-2075.1985.tb03805.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  13. Courtneidge S. A., Heber A. An 81 kd protein complexed with middle T antigen and pp60c-src: a possible phosphatidylinositol kinase. Cell. 1987 Sep 25;50(7):1031–1037. doi: 10.1016/0092-8674(87)90169-3. [DOI] [PubMed] [Google Scholar]
  14. Courtneidge S. A., Smith A. E. Polyoma virus transforming protein associates with the product of the c-src cellular gene. Nature. 1983 Jun 2;303(5916):435–439. doi: 10.1038/303435a0. [DOI] [PubMed] [Google Scholar]
  15. Donoghue D. J., Anderson C., Hunter T., Kaplan P. L. Transmission of the polyoma virus middle T gene as the oncogene of a murine retrovirus. Nature. 1984 Apr 19;308(5961):748–750. doi: 10.1038/308748a0. [DOI] [PubMed] [Google Scholar]
  16. Fluck M. M., Benjamin T. L. Comparisons of two early gene functions essential for transformation in polyoma virus and SV-40. Virology. 1979 Jul 15;96(1):205–228. doi: 10.1016/0042-6822(79)90185-5. [DOI] [PubMed] [Google Scholar]
  17. Gebhardt A., Bell J. C., Foulkes J. G. Abelson transformed fibroblasts lacking the EGF receptor are not tumourigenic in nude mice. EMBO J. 1986 Sep;5(9):2191–2195. doi: 10.1002/j.1460-2075.1986.tb04483.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Gélinas C., Bastin M. Malignant transformation of rat cells by the polyomavirus middle T gene. Virology. 1985 Oct 30;146(2):233–245. doi: 10.1016/0042-6822(85)90007-8. [DOI] [PubMed] [Google Scholar]
  19. Huhn R. D., Posner M. R., Rayter S. I., Foulkes J. G., Frackelton A. R., Jr Cell lines and peripheral blood leukocytes derived from individuals with chronic myelogenous leukemia display virtually identical proteins phosphorylated on tyrosine residues. Proc Natl Acad Sci U S A. 1987 Jul;84(13):4408–4412. doi: 10.1073/pnas.84.13.4408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  20. Hunter T. A tail of two src's: mutatis mutandis. Cell. 1987 Apr 10;49(1):1–4. doi: 10.1016/0092-8674(87)90745-8. [DOI] [PubMed] [Google Scholar]
  21. Kaplan D. R., Whitman M., Schaffhausen B., Pallas D. C., White M., Cantley L., Roberts T. M. Common elements in growth factor stimulation and oncogenic transformation: 85 kd phosphoprotein and phosphatidylinositol kinase activity. Cell. 1987 Sep 25;50(7):1021–1029. doi: 10.1016/0092-8674(87)90168-1. [DOI] [PubMed] [Google Scholar]
  22. Kaplan D. R., Whitman M., Schaffhausen B., Raptis L., Garcea R. L., Pallas D., Roberts T. M., Cantley L. Phosphatidylinositol metabolism and polyoma-mediated transformation. Proc Natl Acad Sci U S A. 1986 Jun;83(11):3624–3628. doi: 10.1073/pnas.83.11.3624. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Kaplan P. L., Ozanne B. Polyoma virus-transformed cells produce transforming growth factor(s) and grow in serum-free medium. Virology. 1982 Dec;123(2):372–380. doi: 10.1016/0042-6822(82)90270-7. [DOI] [PubMed] [Google Scholar]
  24. Land H., Parada L. F., Weinberg R. A. Tumorigenic conversion of primary embryo fibroblasts requires at least two cooperating oncogenes. Nature. 1983 Aug 18;304(5927):596–602. doi: 10.1038/304596a0. [DOI] [PubMed] [Google Scholar]
  25. Liang T. J., Carmichael G. G., Benjamin T. L. A polyoma mutant that encodes small T antigen but not middle T antigen demonstrates uncoupling of cell surface and cytoskeletal changes associated with cell transformation. Mol Cell Biol. 1984 Dec;4(12):2774–2783. doi: 10.1128/mcb.4.12.2774. [DOI] [PMC free article] [PubMed] [Google Scholar]
  26. Noda T., Satake M., Yamaguchi Y., Ito Y. Cooperation of middle and small T antigens of polyomavirus in transformation of established fibroblast and epithelial-like cell lines. J Virol. 1987 Jul;61(7):2253–2263. doi: 10.1128/jvi.61.7.2253-2263.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
  27. Priehs C., Friderici K., Winberry L., Fluck M. M. Properties of cells transformed by the middle T-antigen-coding region of polyomavirus. J Virol. 1986 Jan;57(1):211–218. doi: 10.1128/jvi.57.1.211-218.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  28. Raptis L., Bell J., Whitfield J. F. Protein kinase C increases the activity of the polyoma virus middle T antigen-associated phosphatidylinositol kinase. Biochem Biophys Res Commun. 1988 Jul 15;154(1):306–311. doi: 10.1016/0006-291x(88)90685-7. [DOI] [PubMed] [Google Scholar]
  29. Raptis L., Lamfrom H., Benjamin T. L. Regulation of cellular phenotype and expression of polyomavirus middle T antigen in rat fibroblasts. Mol Cell Biol. 1985 Sep;5(9):2476–2486. doi: 10.1128/mcb.5.9.2476. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Rassoulzadegan M., Cowie A., Carr A., Glaichenhaus N., Kamen R., Cuzin F. The roles of individual polyoma virus early proteins in oncogenic transformation. Nature. 1982 Dec 23;300(5894):713–718. doi: 10.1038/300713a0. [DOI] [PubMed] [Google Scholar]
  31. Rassoulzadegan M., Gaudray P., Canning M., Trejo-Avila L., Cuzin F. Two polyoma virus gene functions involved in the expression of the transformed phenotype in FR 3T3 rat cells. I. Localization of a transformation maintenance function in the proximal half of the large T coding region. Virology. 1981 Oct 30;114(2):489–500. doi: 10.1016/0042-6822(81)90228-2. [DOI] [PubMed] [Google Scholar]
  32. Schaffhausen B., Benjamin T. L. Comparison of phosphorylation of two polyoma virus middle T antigens in vivo and in vitro. J Virol. 1981 Oct;40(1):184–196. doi: 10.1128/jvi.40.1.184-196.1981. [DOI] [PMC free article] [PubMed] [Google Scholar]
  33. Treisman R., Novak U., Favaloro J., Kamen R. Transformation of rat cells by an altered polyoma virus genome expressing only the middle-T protein. Nature. 1981 Aug 13;292(5824):595–600. doi: 10.1038/292595a0. [DOI] [PubMed] [Google Scholar]
  34. Whitman M., Downes C. P., Keeler M., Keller T., Cantley L. Type I phosphatidylinositol kinase makes a novel inositol phospholipid, phosphatidylinositol-3-phosphate. Nature. 1988 Apr 14;332(6165):644–646. doi: 10.1038/332644a0. [DOI] [PubMed] [Google Scholar]
  35. Whitman M., Kaplan D., Roberts T., Cantley L. Evidence for two distinct phosphatidylinositol kinases in fibroblasts. Implications for cellular regulation. Biochem J. 1987 Oct 1;247(1):165–174. doi: 10.1042/bj2470165. [DOI] [PMC free article] [PubMed] [Google Scholar]

Articles from Journal of Virology are provided here courtesy of American Society for Microbiology (ASM)

RESOURCES