Skip to main content
NCBI home page
Journal of Virology logoLink to Journal of Virology
. 1988 Jul;62(7):2444–2452. doi: 10.1128/jvi.62.7.2444-2452.1988

Molecular characterization of three erbB transducing viruses generated during avian leukosis virus-induced erythroleukemia: extensive internal deletion near the kinase domain activates the fibrosarcoma- and hemangioma-inducing potentials of erbB.

M A Raines 1, N J Maihle 1, C Moscovici 1, M G Moscovici 1, H J Kung 1
PMCID: PMC253403  PMID: 2836624

Abstract

Three new erbB transducing viruses generated during avian leukosis virus-induced erythroblastosis have been cloned and sequenced, and their transforming abilities have been analyzed. Provirus 9134 E1 expresses an amino-terminally truncated erbB product that is analogous to the proviral insertionally activated c-erbB gag-erbB fusion product. This virus efficiently induces erythroblastosis, but does not transform fibroblasts in vitro or induce sarcomas in vivo. In contrast, virus 9134 S3 expresses an erbB product identical to the erbB product of 9134 E1, with the exception of a large internal deletion located between the kinase domain and the putative autophosphorylation site, P1. Interestingly, this virus is no longer capable of inducing erythroblastosis, but can induce both fibrosarcomas and hemangiomas in vivo. Provirus 9134 F3 has sustained an approximately 23-amino-acid carboxy-terminal truncation and is capable of inducing both erythroblastosis and sarcomagenesis. This virus expresses an erbB product with the shortest carboxy-terminal truncation sufficient to reveal the sarcomagenic potential of this protein. The distinct transforming properties of these viruses indicate that different structural domains of the erbB product confer distinct disease specificities.

Full text

PDF
2444

Images in this article

2446Image
on p.2446
2447Image
on p.2447
2449Image
on p.2449

Selected References

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

  1. Aviv H., Leder P. Purification of biologically active globin messenger RNA by chromatography on oligothymidylic acid-cellulose. Proc Natl Acad Sci U S A. 1972 Jun;69(6):1408–1412. doi: 10.1073/pnas.69.6.1408. [DOI] [PMC free article] [PubMed] [Google Scholar]
  2. Beug H., Hayman M. J., Raines M. B., Kung H. J., Vennström B. Rous-associated virus 1-induced erythroleukemic cells exhibit a weakly transformed phenotype in vitro and release c-erbB-containing retroviruses unable to transform fibroblasts. J Virol. 1986 Mar;57(3):1127–1138. doi: 10.1128/jvi.57.3.1127-1138.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
  3. Beug H., Hayman M. J. Temperature-sensitive mutants of avian erythroblastosis virus: surface expression of the erbB product correlates with transformation. Cell. 1984 Apr;36(4):963–972. doi: 10.1016/0092-8674(84)90046-1. [DOI] [PubMed] [Google Scholar]
  4. Cartwright C. A., Eckhart W., Simon S., Kaplan P. L. Cell transformation by pp60c-src mutated in the carboxy-terminal regulatory domain. Cell. 1987 Apr 10;49(1):83–91. doi: 10.1016/0092-8674(87)90758-6. [DOI] [PubMed] [Google Scholar]
  5. Choi O. R., Trainor C., Graf T., Beug H., Engel J. D. A single amino acid substitution in v-erbB confers a thermolabile phenotype to ts167 avian erythroblastosis virus-transformed erythroid cells. Mol Cell Biol. 1986 May;6(5):1751–1759. doi: 10.1128/mcb.6.5.1751. [DOI] [PMC free article] [PubMed] [Google Scholar]
  6. Damm K., Beug H., Graf T., Vennström B. A single point mutation in erbA restores the erythroid transforming potential of a mutant avian erythroblastosis virus (AEV) defective in both erbA and erbB oncogenes. EMBO J. 1987 Feb;6(2):375–382. doi: 10.1002/j.1460-2075.1987.tb04765.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
  7. Downward J., Parker P., Waterfield M. D. Autophosphorylation sites on the epidermal growth factor receptor. Nature. 1984 Oct 4;311(5985):483–485. doi: 10.1038/311483a0. [DOI] [PubMed] [Google Scholar]
  8. Fung Y. K., Lewis W. G., Crittenden L. B., Kung H. J. Activation of the cellular oncogene c-erbB by LTR insertion: molecular basis for induction of erythroblastosis by avian leukosis virus. Cell. 1983 Jun;33(2):357–368. doi: 10.1016/0092-8674(83)90417-8. [DOI] [PubMed] [Google Scholar]
  9. Gamett D. C., Tracy S. E., Robinson H. L. Differences in sequences encoding the carboxyl-terminal domain of the epidermal growth factor receptor correlate with differences in the disease potential of viral erbB genes. Proc Natl Acad Sci U S A. 1986 Aug;83(16):6053–6057. doi: 10.1073/pnas.83.16.6053. [DOI] [PMC free article] [PubMed] [Google Scholar]
  10. Graham F. L., van der Eb A. J. A new technique for the assay of infectivity of human adenovirus 5 DNA. Virology. 1973 Apr;52(2):456–467. doi: 10.1016/0042-6822(73)90341-3. [DOI] [PubMed] [Google Scholar]
  11. Hunter E., Hill E., Hardwick M., Bhown A., Schwartz D. E., Tizard R. Complete sequence of the Rous sarcoma virus env gene: identification of structural and functional regions of its product. J Virol. 1983 Jun;46(3):920–936. doi: 10.1128/jvi.46.3.920-936.1983. [DOI] [PMC free article] [PubMed] [Google Scholar]
  12. Jansson M., Beug H., Gray C., Graf T., Vennström B. Defective v-erbB genes can be complemented by v-erbA in erythroblast and fibroblast transformation. Oncogene. 1987 May;1(2):167–173. [PubMed] [Google Scholar]
  13. Kato J. Y., Takeya T., Grandori C., Iba H., Levy J. B., Hanafusa H. Amino acid substitutions sufficient to convert the nontransforming p60c-src protein to a transforming protein. Mol Cell Biol. 1986 Dec;6(12):4155–4160. doi: 10.1128/mcb.6.12.4155. [DOI] [PMC free article] [PubMed] [Google Scholar]
  14. Kmiecik T. E., Shalloway D. Activation and suppression of pp60c-src transforming ability by mutation of its primary sites of tyrosine phosphorylation. Cell. 1987 Apr 10;49(1):65–73. doi: 10.1016/0092-8674(87)90756-2. [DOI] [PubMed] [Google Scholar]
  15. Kornbluth S., Sudol M., Hanafusa H. Association of the polyomavirus middle-T antigen with c-yes protein. Nature. 1987 Jan 8;325(7000):171–173. doi: 10.1038/325171a0. [DOI] [PubMed] [Google Scholar]
  16. Levy J. B., Iba H., Hanafusa H. Activation of the transforming potential of p60c-src by a single amino acid change. Proc Natl Acad Sci U S A. 1986 Jun;83(12):4228–4232. doi: 10.1073/pnas.83.12.4228. [DOI] [PMC free article] [PubMed] [Google Scholar]
  17. Miles B. D., Robinson H. L. High-frequency transduction of c-erbB in avian leukosis virus-induced erythroblastosis. J Virol. 1985 May;54(2):295–303. doi: 10.1128/jvi.54.2.295-303.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  18. Moscovici C., Moscovici M. G., Jimenez H., Lai M. M., Hayman M. J., Vogt P. K. Continuous tissue culture cell lines derived from chemically induced tumors of Japanese quail. Cell. 1977 May;11(1):95–103. doi: 10.1016/0092-8674(77)90320-8. [DOI] [PubMed] [Google Scholar]
  19. Nilsen T. W., Maroney P. A., Goodwin R. G., Rottman F. M., Crittenden L. B., Raines M. A., Kung H. J. c-erbB activation in ALV-induced erythroblastosis: novel RNA processing and promoter insertion result in expression of an amino-truncated EGF receptor. Cell. 1985 Jul;41(3):719–726. doi: 10.1016/s0092-8674(85)80052-0. [DOI] [PubMed] [Google Scholar]
  20. Pelley R. J., Moscovici C., Hughes S., Kung H. J. Proviral-activated c-erbB is leukemogenic but not sarcomagenic: characterization of a replication-competent retrovirus containing the activated c-erbB. J Virol. 1988 May;62(5):1840–1844. doi: 10.1128/jvi.62.5.1840-1844.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  21. Piwnica-Worms H., Saunders K. B., Roberts T. M., Smith A. E., Cheng S. H. Tyrosine phosphorylation regulates the biochemical and biological properties of pp60c-src. Cell. 1987 Apr 10;49(1):75–82. doi: 10.1016/0092-8674(87)90757-4. [DOI] [PubMed] [Google Scholar]
  22. Radinsky R., Kraemer P. M., Raines M. A., Kung H. J., Culp L. A. Amplification and rearrangement of the Kirsten ras oncogene in virus-transformed BALB/c 3T3 cells during malignant tumor progression. Proc Natl Acad Sci U S A. 1987 Aug;84(15):5143–5147. doi: 10.1073/pnas.84.15.5143. [DOI] [PMC free article] [PubMed] [Google Scholar]
  23. Raines M. A., Lewis W. G., Crittenden L. B., Kung H. J. c-erbB activation in avian leukosis virus-induced erythroblastosis: clustered integration sites and the arrangement of provirus in the c-erbB alleles. Proc Natl Acad Sci U S A. 1985 Apr;82(8):2287–2291. doi: 10.1073/pnas.82.8.2287. [DOI] [PMC free article] [PubMed] [Google Scholar]
  24. Raines M. A., Maihle N. J., Moscovici C., Crittenden L., Kung H. J. Mechanism of c-erbB transduction: newly released transducing viruses retain poly(A) tracts of erbB transcripts and encode C-terminally intact erbB proteins. J Virol. 1988 Jul;62(7):2437–2443. doi: 10.1128/jvi.62.7.2437-2443.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
  25. 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]
  26. Sealy L., Moscovici G., Moscovici C., Bishop J. M. Site-specific mutagenesis of avian erythroblastosis virus: v-erb-A is not required for transformation of fibroblasts. Virology. 1983 Oct 15;130(1):179–194. doi: 10.1016/0042-6822(83)90126-5. [DOI] [PubMed] [Google Scholar]
  27. Sealy L., Privalsky M. L., Moscovici G., Moscovici C., Bishop J. M. Site-specific mutagenesis of avian erythroblastosis virus: erb-B is required for oncogenicity. Virology. 1983 Oct 15;130(1):155–178. doi: 10.1016/0042-6822(83)90125-3. [DOI] [PubMed] [Google Scholar]
  28. Southern P. J., Berg P. Transformation of mammalian cells to antibiotic resistance with a bacterial gene under control of the SV40 early region promoter. J Mol Appl Genet. 1982;1(4):327–341. [PubMed] [Google Scholar]
  29. Tracy S. E., Woda B. A., Robinson H. L. Induction of angiosarcoma by a c-erbB transducing virus. J Virol. 1985 May;54(2):304–310. doi: 10.1128/jvi.54.2.304-310.1985. [DOI] [PMC free article] [PubMed] [Google Scholar]
  30. Yamamoto T., Hihara H., Nishida T., Kawai S., Toyoshima K. A new avian erythroblastosis virus, AEV-H, carries erbB gene responsible for the induction of both erythroblastosis and sarcomas. Cell. 1983 Aug;34(1):225–232. doi: 10.1016/0092-8674(83)90153-8. [DOI] [PubMed] [Google Scholar]
  31. Yamamoto T., Nishida T., Miyajima N., Kawai S., Ooi T., Toyoshima K. The erbB gene of avian erythroblastosis virus is a member of the src gene family. Cell. 1983 Nov;35(1):71–78. doi: 10.1016/0092-8674(83)90209-x. [DOI] [PubMed] [Google Scholar]

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

RESOURCES