Abstract
The Tpl-2 locus, cloned by provirus tagging from one of three sublines of the Moloney leukemia virus-induced rat thymoma 2769, defines a gene encoding a protein kinase associated with progression in 22.5% of the tumors. Tpl-2 is expressed primarily in spleen, thymus, liver, and lung. Provirus integration occurs in the last intron of the gene, leading to the expression of a truncated mRNA that terminates in the proviral long terminal repeat and encodes a protein with an altered C-terminal domain. Strong evidence that this genetic change confers growth advantage to affected cell clones was provided by the finding that, during cultivation of all three sublines derived from tumor 2769, cells were selected that harbored independent provirus insertions in the Tpl-2 locus. Exposure of normal rat spleen cells to Con A induces the expression of enhanced levels of Tpl-2 within the first 60 min from the time of exposure suggesting that, in normal splenocytes, Tpl-2 may be involved in the transition from a quiescent to the G1 phase of the cell cycle.
Full text
PDF![2251](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f0/46064/de47c9fe60dd/pnas01465-0162.png)
![2252](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f0/46064/ed8cf94b9ffb/pnas01465-0163.png)
![2253](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f0/46064/fe33ddd9c115/pnas01465-0164.png)
![2254](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f0/46064/0b11fc83d49a/pnas01465-0165.png)
![2255](https://cdn.ncbi.nlm.nih.gov/pmc/blobs/f6f0/46064/3219ef0ec647/pnas01465-0166.png)
Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Barker C. S., Bear S. E., Keler T., Copeland N. G., Gilbert D. J., Jenkins N. A., Yeung R. S., Tsichlis P. N. Activation of the prolactin receptor gene by promoter insertion in a Moloney murine leukemia virus-induced rat thymoma. J Virol. 1992 Nov;66(11):6763–6768. doi: 10.1128/jvi.66.11.6763-6768.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bear S. E., Bellacosa A., Lazo P. A., Jenkins N. A., Copeland N. G., Hanson C., Levan G., Tsichlis P. N. Provirus insertion in Tpl-1, an Ets-1-related oncogene, is associated with tumor progression in Moloney murine leukemia virus-induced rat thymic lymphomas. Proc Natl Acad Sci U S A. 1989 Oct;86(19):7495–7499. doi: 10.1073/pnas.86.19.7495. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Davison A. J., Scott J. E. The complete DNA sequence of varicella-zoster virus. J Gen Virol. 1986 Sep;67(Pt 9):1759–1816. doi: 10.1099/0022-1317-67-9-1759. [DOI] [PubMed] [Google Scholar]
- Dolcetti R., Rizzo S., Viel A., Maestro R., De Re V., Feriotto G., Boiocchi M. N-myc activation by proviral insertion in MCF 247-induced murine T-cell lymphomas. Oncogene. 1989 Aug;4(8):1009–1014. [PubMed] [Google Scholar]
- Flint A. J., Paladini R. D., Koshland D. E., Jr Autophosphorylation of protein kinase C at three separated regions of its primary sequence. Science. 1990 Jul 27;249(4967):408–411. doi: 10.1126/science.2377895. [DOI] [PubMed] [Google Scholar]
- Hanks S. K., Quinn A. M., Hunter T. The protein kinase family: conserved features and deduced phylogeny of the catalytic domains. Science. 1988 Jul 1;241(4861):42–52. doi: 10.1126/science.3291115. [DOI] [PubMed] [Google Scholar]
- Hann S. R., King M. W., Bentley D. L., Anderson C. W., Eisenman R. N. A non-AUG translational initiation in c-myc exon 1 generates an N-terminally distinct protein whose synthesis is disrupted in Burkitt's lymphomas. Cell. 1988 Jan 29;52(2):185–195. doi: 10.1016/0092-8674(88)90507-7. [DOI] [PubMed] [Google Scholar]
- Jones S. W., Erikson E., Blenis J., Maller J. L., Erikson R. L. A Xenopus ribosomal protein S6 kinase has two apparent kinase domains that are each similar to distinct protein kinases. Proc Natl Acad Sci U S A. 1988 May;85(10):3377–3381. doi: 10.1073/pnas.85.10.3377. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Knighton D. R., Zheng J. H., Ten Eyck L. F., Ashford V. A., Xuong N. H., Taylor S. S., Sowadski J. M. Crystal structure of the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase. Science. 1991 Jul 26;253(5018):407–414. doi: 10.1126/science.1862342. [DOI] [PubMed] [Google Scholar]
- Knighton D. R., Zheng J. H., Ten Eyck L. F., Xuong N. H., Taylor S. S., Sowadski J. M. Structure of a peptide inhibitor bound to the catalytic subunit of cyclic adenosine monophosphate-dependent protein kinase. Science. 1991 Jul 26;253(5018):414–420. doi: 10.1126/science.1862343. [DOI] [PubMed] [Google Scholar]
- Koch C. A., Anderson D., Moran M. F., Ellis C., Pawson T. SH2 and SH3 domains: elements that control interactions of cytoplasmic signaling proteins. Science. 1991 May 3;252(5006):668–674. doi: 10.1126/science.1708916. [DOI] [PubMed] [Google Scholar]
- Lazo P. A., Klein-Szanto A. J., Tsichlis P. N. T-cell lymphoma lines derived from rat thymomas induced by Moloney murine leukemia virus: phenotypic diversity and its implications. J Virol. 1990 Aug;64(8):3948–3959. doi: 10.1128/jvi.64.8.3948-3959.1990. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lazo P. A., Tsichlis P. N. Biology and pathogenesis of retroviruses. Semin Oncol. 1990 Jun;17(3):269–294. [PubMed] [Google Scholar]
- Miyoshi J., Higashi T., Mukai H., Ohuchi T., Kakunaga T. Structure and transforming potential of the human cot oncogene encoding a putative protein kinase. Mol Cell Biol. 1991 Aug;11(8):4088–4096. doi: 10.1128/mcb.11.8.4088. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nadin-Davis S. A., Nasim A. A gene which encodes a predicted protein kinase can restore some functions of the ras gene in fission yeast. EMBO J. 1988 Apr;7(4):985–993. doi: 10.1002/j.1460-2075.1988.tb02905.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nicolson G. L. Tumor cell instability, diversification, and progression to the metastatic phenotype: from oncogene to oncofetal expression. Cancer Res. 1987 Mar 15;47(6):1473–1487. [PubMed] [Google Scholar]
- Rajchel A., Chan Y. L., Wool I. G. The primary structure of rat ribosomal protein L32. Nucleic Acids Res. 1988 Mar 25;16(5):2347–2347. doi: 10.1093/nar/16.5.2347. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Selten G., Cuypers H. T., Berns A. Proviral activation of the putative oncogene Pim-1 in MuLV induced T-cell lymphomas. EMBO J. 1985 Jul;4(7):1793–1798. doi: 10.1002/j.1460-2075.1985.tb03852.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Shaw G., Kamen R. A conserved AU sequence from the 3' untranslated region of GM-CSF mRNA mediates selective mRNA degradation. Cell. 1986 Aug 29;46(5):659–667. doi: 10.1016/0092-8674(86)90341-7. [DOI] [PubMed] [Google Scholar]
- Takio K., Blumenthal D. K., Walsh K. A., Titani K., Krebs E. G. Amino acid sequence of rabbit skeletal muscle myosin light chain kinase. Biochemistry. 1986 Dec 2;25(24):8049–8057. doi: 10.1021/bi00372a038. [DOI] [PubMed] [Google Scholar]
- Takio K., Wade R. D., Smith S. B., Krebs E. G., Walsh K. A., Titani K. Guanosine cyclic 3',5'-phosphate dependent protein kinase, a chimeric protein homologous with two separate protein families. Biochemistry. 1984 Aug 28;23(18):4207–4218. doi: 10.1021/bi00313a030. [DOI] [PubMed] [Google Scholar]
- Teague M. A., Chaleff D. T., Errede B. Nucleotide sequence of the yeast regulatory gene STE7 predicts a protein homologous to protein kinases. Proc Natl Acad Sci U S A. 1986 Oct;83(19):7371–7375. doi: 10.1073/pnas.83.19.7371. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Tsichlis P. N., Strauss P. G., Hu L. F. A common region for proviral DNA integration in MoMuLV-induced rat thymic lymphomas. 1983 Mar 31-Apr 6Nature. 302(5907):445–449. doi: 10.1038/302445a0. [DOI] [PubMed] [Google Scholar]
- Uhler M. D., Carmichael D. F., Lee D. C., Chrivia J. C., Krebs E. G., McKnight G. S. Isolation of cDNA clones coding for the catalytic subunit of mouse cAMP-dependent protein kinase. Proc Natl Acad Sci U S A. 1986 Mar;83(5):1300–1304. doi: 10.1073/pnas.83.5.1300. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Watson R., Oskarsson M., Vande Woude G. F. Human DNA sequence homologous to the transforming gene (mos) of Moloney murine sarcoma virus. Proc Natl Acad Sci U S A. 1982 Jul;79(13):4078–4082. doi: 10.1073/pnas.79.13.4078. [DOI] [PMC free article] [PubMed] [Google Scholar]