Abstract
Mink cells nonproductively-infected with the weakly-transforming T-8 isolate of murine leukemia virus (MuLV) express a 110,000 mol wt polyprotein designated T-8 P110. By immunoprecipitation analysis, T-8 P110 is shown to contain AKR-MuLV amino terminal gag gene-specific components (p15, p12) but to lack p30, p10, gp70, and p15(E) antigenic determinants. These observations are further substantiated by tryptic peptide analysis indicating T-8 P110 to share approximately six lysine- containing tryptic peptides with AKR-MuLV Pr65gag, and none with AKr- MuLV Pr82env. Furthermore, of seven methionine-containing T-8 P110 tryptic peptides, at least four can be conclusively shown not to be present in either AKr-MuLV Pr180gag/pol or Pr82env. A clonal mink cell line nonproductively infected by T-8, and expressing high levels of P110, although not morphologically transformed, is shown to lack elevated levels of tyrosine-specific protein kinase activity and reduction of epidermal growth factor binding sites characteristic of cells transformed by many other RNA-transforming viruses. These findings argue either that the T-8 viral genome contains acquired cellular sequences encoding a portion of P110, or that T-8 P110 represents an inphase deletion of AKR-MuLV Pr180gag/pol with extensive posttranlational modification and that an as yet unidentified protein is responsible for T-8 associated transformation.
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- Blomberg J., Reynolds F. H., Jr, Van de Ven W. J., Stephenson J. R. Abelson murine leukaemia virus transformation involves loss of epidermal growth factor-binding sites. Nature. 1980 Jul 31;286(5772):504–507. doi: 10.1038/286504a0. [DOI] [PubMed] [Google Scholar]
- Collett M. S., Erikson R. L. Protein kinase activity associated with the avian sarcoma virus src gene product. Proc Natl Acad Sci U S A. 1978 Apr;75(4):2021–2024. doi: 10.1073/pnas.75.4.2021. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Duesberg P. H., Vogt P. K. Avian acute leukemia viruses MC29 and MH2 share specific RNA sequences: evidence for a second class of transforming genes. Proc Natl Acad Sci U S A. 1979 Apr;76(4):1633–1637. doi: 10.1073/pnas.76.4.1633. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Elder J. H., Gautsch J. W., Jensen F. C., Lerner R. A., Hartley J. W., Rowe W. P. Biochemical evidence that MCF murine leukemia viruses are envelope (env) gene recombinants. Proc Natl Acad Sci U S A. 1977 Oct;74(10):4676–4680. doi: 10.1073/pnas.74.10.4676. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hartley J. W., Wolford N. K., Old L. J., Rowe W. P. A new class of murine leukemia virus associated with development of spontaneous lymphomas. Proc Natl Acad Sci U S A. 1977 Feb;74(2):789–792. doi: 10.1073/pnas.74.2.789. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hunter T., Sefton B. M. Transforming gene product of Rous sarcoma virus phosphorylates tyrosine. Proc Natl Acad Sci U S A. 1980 Mar;77(3):1311–1315. doi: 10.1073/pnas.77.3.1311. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Kawashima K., Ikeda H., Hartley J. W., Stockert E., Rowe W. P., Old L. J. Changes in expression of murine leukemia virus antigens and production of xenotropic virus in the late preleukemic period in AKR mice. Proc Natl Acad Sci U S A. 1976 Dec;73(12):4680–4684. doi: 10.1073/pnas.73.12.4680. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Levinson A. D., Oppermann H., Levintow L., Varmus H. E., Bishop J. M. Evidence that the transforming gene of avian sarcoma virus encodes a protein kinase associated with a phosphoprotein. Cell. 1978 Oct;15(2):561–572. doi: 10.1016/0092-8674(78)90024-7. [DOI] [PubMed] [Google Scholar]
- Oroszlan S., Henderson L. E., Stephenson J. R., Copeland T. D., Long C. W., Ihle J. N., Gilden R. V. Amino- and carboxyl-terminal amino acid sequences of proteins coded by gag gene of murine leukemia virus. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1404–1408. doi: 10.1073/pnas.75.3.1404. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Porzig K. J., Robbins K. C., Aaronson S. A. Cellular regulation of mammalian sarcoma virus expression: a gene regulation model for oncogenesis. Cell. 1979 Apr;16(4):875–884. doi: 10.1016/0092-8674(79)90102-8. [DOI] [PubMed] [Google Scholar]
- Reynolds F. H., Jr, Sacks T. L., Deobagkar D. N., Stephenson J. R. Cells nonproductively transformed by Abelson murine leukemia virus express a high molecular weight polyprotein containing structural and nonstructural components. Proc Natl Acad Sci U S A. 1978 Aug;75(8):3974–3978. doi: 10.1073/pnas.75.8.3974. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reynolds F. H., Jr, Van de Ven W. J., Stephenson J. R. Abelson murine leukemia virus transformation-defective mutants with impaired P120-associated protein kinase activity. J Virol. 1980 Nov;36(2):374–386. doi: 10.1128/jvi.36.2.374-386.1980. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Reynolds R. K., van de Ven W. J., Stephenson J. R. Translation of type C viral RNAs in Xenopus laevis oocytes: evidence that the 120,000-molecular-weight polyprotein expressed in Abelson leukemia virus-transformed cells is virus coded. J Virol. 1978 Nov;28(2):665–670. doi: 10.1128/jvi.28.2.665-670.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Rommelaere J., Faller D. V., Hopkins N. Characterization and mapping of RNase T1-resistant oligonucleotides derived from the genomes of Akv and MCF murine leukemia viruses. Proc Natl Acad Sci U S A. 1978 Jan;75(1):495–499. doi: 10.1073/pnas.75.1.495. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sacks T. L., Hershey E. J., Stephenson J. R. Abelson murine leukemia virus-infected cell lines defective in transformation. Virology. 1979 Sep;97(2):231–240. doi: 10.1016/0042-6822(79)90335-0. [DOI] [PubMed] [Google Scholar]
- Sacks T. L., Reynolds F. H., Jr, Deobagkar D. N., Stephenson J. R. Murine leukemia virus (T-8)-transformed cells: identification of a precursor polyprotein containing gag gene-coded proteins (p15 and p12) and a nonstructural component. J Virol. 1978 Sep;27(3):809–814. doi: 10.1128/jvi.27.3.809-814.1978. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Scolnick E. M., Rands E., Williams D., Parks W. P. Studies on the nucleic acid sequences of Kirsten sarcoma virus: a model for formation of a mammalian RNA-containing sarcoma virus. J Virol. 1973 Sep;12(3):458–463. doi: 10.1128/jvi.12.3.458-463.1973. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Sefton B. M., Hunter T., Beemon K., Eckhart W. Evidence that the phosphorylation of tyrosine is essential for cellular transformation by Rous sarcoma virus. Cell. 1980 Jul;20(3):807–816. doi: 10.1016/0092-8674(80)90327-x. [DOI] [PubMed] [Google Scholar]
- Sherr C. J., Sen A., Todaro G. J., Sliski A., Essex M. Pseudotypes of feline sarcoma virus contain an 85,000-dalton protein with feline oncornavirus-associated cell membrane antigen (FOCMA) activity. Proc Natl Acad Sci U S A. 1978 Mar;75(3):1505–1509. doi: 10.1073/pnas.75.3.1505. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Staal S. P., Hartley J. W., Rowe W. P. Isolation of transforming murine leukemia viruses from mice with a high incidence of spontaneous lymphoma. Proc Natl Acad Sci U S A. 1977 Jul;74(7):3065–3067. doi: 10.1073/pnas.74.7.3065. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stehelin D., Varmus H. E., Bishop J. M., Vogt P. K. DNA related to the transforming gene(s) of avian sarcoma viruses is present in normal avian DNA. Nature. 1976 Mar 11;260(5547):170–173. doi: 10.1038/260170a0. [DOI] [PubMed] [Google Scholar]
- Stephenson J. R., Khan A. S., Sliski A. H., Essex M. Feline oncornavirus-associated cell membrane antigen: evidence for an immunologically crossreactive feline sarcoma virus-coded protein. Proc Natl Acad Sci U S A. 1977 Dec;74(12):5608–5612. doi: 10.1073/pnas.74.12.5608. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Stephenson J. R., Khan A. S., van de Ven W. J., Reynolds F. H., Jr Type C retroviruses as vectors for cloning cellular genes with probable transforming function. J Natl Cancer Inst. 1979 Nov;63(5):1111–1119. [PubMed] [Google Scholar]
- Stephenson J. R., Reynolds R. K., Devare S. G., Reynolds F. H. Biochemical and immunological properties of gag genecoded structural proteins of endogenous tyep C RNA tumor viruses of diverse mammalian species. J Biol Chem. 1977 Nov 10;252(21):7818–7825. [PubMed] [Google Scholar]
- Todaro G. J., De Larco J. E. Growth factors produced by sarcoma virus-transformed cells. Cancer Res. 1978 Nov;38(11 Pt 2):4147–4154. [PubMed] [Google Scholar]
- Van de Ven W. J., Reynolds F. H., Jr, Nalewaik R. P., Stephenson J. R. The nonstructural component of the Abelson murine leukemia virus polyprotein P120 is encoded by newly acquired genetic sequences. J Virol. 1979 Dec;32(3):1041–1045. doi: 10.1128/jvi.32.3.1041-1045.1979. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Van de Ven W. J., Reynolds F. H., Jr, Stephenson J. R. The nonstructural components of polyproteins encoded by replication-defective mammalian transforming retroviruses are phosphorylated and have associated protein kinase activity. Virology. 1980 Feb;101(1):185–197. doi: 10.1016/0042-6822(80)90495-x. [DOI] [PubMed] [Google Scholar]
- Witte O. N., Dasgupta A., Baltimore D. Abelson murine leukaemia virus protein is phosphorylated in vitro to form phosphotyrosine. Nature. 1980 Feb 28;283(5750):826–831. doi: 10.1038/283826a0. [DOI] [PubMed] [Google Scholar]
- Witte O. N., Rosenberg N., Paskind M., Shields A., Baltimore D. Identification of an Abelson murine leukemia virus-encoded protein present in transformed fibroblast and lymphoid cells. Proc Natl Acad Sci U S A. 1978 May;75(5):2488–2492. doi: 10.1073/pnas.75.5.2488. [DOI] [PMC free article] [PubMed] [Google Scholar]
