Abstract
The human T-cell- or lymphocyte-specific gene, lck, encodes a tyrosine kinase and is a member of the src family. In this report we demonstrate that there are two classes of human lck transcripts (types I and II), containing different 5'-untranslated regions, which are expressed from two distinct promoters. No apparent sequence similarity was observed between the 5'-flanking regions of the two promoters. The expression of lck in human T-cell leukemia and carcinoma cell lines and in human peripheral blood T lymphocytes was examined by S1 nuclease and primer extension mapping and by Northern (RNA) blot analysis of total cellular RNA. The following results were obtained. (i) Two RNA start sites in the downstream promoter were used to generate type I transcripts. (ii) The major human type I start site has not been described for the mouse. (iii) At least five RNA start sites in the upstream promoter were used to generate type II transcripts. (iv) In T cells and in two colon carcinoma cell lines, type II transcripts were present in higher amounts than type I transcripts. (v) In T cells treated with phytohemagglutinin, tetradecanoylphorbol acetate, and cyclosporin A, the modulation of lck expression was associated primarily with changes in levels of type II transcripts. The above results suggest that the two human lck promoters are utilized differentially and may be regulated independently during certain physiological states.
Full text
PDF







Images in this article
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Adachi A., Koenig S., Gendelman H. E., Daugherty D., Gattoni-Celli S., Fauci A. S., Martin M. A. Productive, persistent infection of human colorectal cell lines with human immunodeficiency virus. J Virol. 1987 Jan;61(1):209–213. doi: 10.1128/jvi.61.1.209-213.1987. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Adler H. T., Reynolds P. J., Kelley C. M., Sefton B. M. Transcriptional activation of lck by retrovirus promoter insertion between two lymphoid-specific promoters. J Virol. 1988 Nov;62(11):4113–4122. doi: 10.1128/jvi.62.11.4113-4122.1988. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Bishop J. M. Viral oncogenes. Cell. 1985 Aug;42(1):23–38. doi: 10.1016/s0092-8674(85)80098-2. [DOI] [PubMed] [Google Scholar]
- Breathnach R., Chambon P. Organization and expression of eucaryotic split genes coding for proteins. Annu Rev Biochem. 1981;50:349–383. doi: 10.1146/annurev.bi.50.070181.002025. [DOI] [PubMed] [Google Scholar]
- 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]
- Elliott J. F., Lin Y., Mizel S. B., Bleackley R. C., Harnish D. G., Paetkau V. Induction of interleukin 2 messenger RNA inhibited by cyclosporin A. Science. 1984 Dec 21;226(4681):1439–1441. doi: 10.1126/science.6334364. [DOI] [PubMed] [Google Scholar]
- Frederickson R. M., Micheau M. R., Iwamoto A., Miyamoto N. G. 5' flanking and first intron sequences of the human beta-actin gene required for efficient promoter activity. Nucleic Acids Res. 1989 Jan 11;17(1):253–270. doi: 10.1093/nar/17.1.253. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Garvin A. M., Pawar S., Marth J. D., Perlmutter R. M. Structure of the murine lck gene and its rearrangement in a murine lymphoma cell line. Mol Cell Biol. 1988 Aug;8(8):3058–3064. doi: 10.1128/mcb.8.8.3058. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Hunter T., Cooper J. A. Protein-tyrosine kinases. Annu Rev Biochem. 1985;54:897–930. doi: 10.1146/annurev.bi.54.070185.004341. [DOI] [PubMed] [Google Scholar]
- Koga Y., Caccia N., Toyonaga B., Spolski R., Yanagi Y., Yoshikai Y., Mak T. W. A human T cell-specific cDNA clone (YT16) encodes a protein with extensive homology to a family of protein-tyrosine kinases. Eur J Immunol. 1986 Dec;16(12):1643–1646. doi: 10.1002/eji.1830161229. [DOI] [PubMed] [Google Scholar]
- Koga Y., Kimura N., Minowada J., Mak T. W. Expression of the human T-cell-specific tyrosine kinase YT16 (lck) message in leukemic T-cell lines. Cancer Res. 1988 Feb 15;48(4):856–859. [PubMed] [Google Scholar]
- Krönke M., Leonard W. J., Depper J. M., Arya S. K., Wong-Staal F., Gallo R. C., Waldmann T. A., Greene W. C. Cyclosporin A inhibits T-cell growth factor gene expression at the level of mRNA transcription. Proc Natl Acad Sci U S A. 1984 Aug;81(16):5214–5218. doi: 10.1073/pnas.81.16.5214. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Maniatis T., Hardison R. C., Lacy E., Lauer J., O'Connell C., Quon D., Sim G. K., Efstratiadis A. The isolation of structural genes from libraries of eucaryotic DNA. Cell. 1978 Oct;15(2):687–701. doi: 10.1016/0092-8674(78)90036-3. [DOI] [PubMed] [Google Scholar]
- Marth J. D., Cooper J. A., King C. S., Ziegler S. F., Tinker D. A., Overell R. W., Krebs E. G., Perlmutter R. M. Neoplastic transformation induced by an activated lymphocyte-specific protein tyrosine kinase (pp56lck). Mol Cell Biol. 1988 Feb;8(2):540–550. doi: 10.1128/mcb.8.2.540. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marth J. D., Lewis D. B., Wilson C. B., Gearn M. E., Krebs E. G., Perlmutter R. M. Regulation of pp56lck during T-cell activation: functional implications for the src-like protein tyrosine kinases. EMBO J. 1987 Sep;6(9):2727–2734. doi: 10.1002/j.1460-2075.1987.tb02566.x. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Marth J. D., Overell R. W., Meier K. E., Krebs E. G., Perlmutter R. M. Translational activation of the lck proto-oncogene. Nature. 1988 Mar 10;332(6160):171–173. doi: 10.1038/332171a0. [DOI] [PubMed] [Google Scholar]
- Marth J. D., Peet R., Krebs E. G., Perlmutter R. M. A lymphocyte-specific protein-tyrosine kinase gene is rearranged and overexpressed in the murine T cell lymphoma LSTRA. Cell. 1985 Dec;43(2 Pt 1):393–404. doi: 10.1016/0092-8674(85)90169-2. [DOI] [PubMed] [Google Scholar]
- 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]
- Sharp P. A. Speculations on RNA splicing. Cell. 1981 Mar;23(3):643–646. doi: 10.1016/0092-8674(81)90425-6. [DOI] [PubMed] [Google Scholar]
- Veillette A., Bookman M. A., Horak E. M., Bolen J. B. The CD4 and CD8 T cell surface antigens are associated with the internal membrane tyrosine-protein kinase p56lck. Cell. 1988 Oct 21;55(2):301–308. doi: 10.1016/0092-8674(88)90053-0. [DOI] [PubMed] [Google Scholar]
- Veillette A., Foss F. M., Sausville E. A., Bolen J. B., Rosen N. Expression of the lck tyrosine kinase gene in human colon carcinoma and other non-lymphoid human tumor cell lines. Oncogene Res. 1987 Sep-Oct;1(4):357–374. [PubMed] [Google Scholar]
- Veillette A., Horak I. D., Horak E. M., Bookman M. A., Bolen J. B. Alterations of the lymphocyte-specific protein tyrosine kinase (p56lck) during T-cell activation. Mol Cell Biol. 1988 Oct;8(10):4353–4361. doi: 10.1128/mcb.8.10.4353. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Voronova A. F., Adler H. T., Sefton B. M. Two lck transcripts containing different 5' untranslated regions are present in T cells. Mol Cell Biol. 1987 Dec;7(12):4407–4413. doi: 10.1128/mcb.7.12.4407. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Voronova A. F., Sefton B. M. Expression of a new tyrosine protein kinase is stimulated by retrovirus promoter insertion. Nature. 1986 Feb 20;319(6055):682–685. doi: 10.1038/319682a0. [DOI] [PubMed] [Google Scholar]
- Wasylyk B., Kédinger C., Corden J., Brison O., Chambon P. Specific in vitro initiation of transcription on conalbumin and ovalbumin genes and comparison with adenovirus-2 early and late genes. Nature. 1980 Jun 5;285(5764):367–373. doi: 10.1038/285367a0. [DOI] [PubMed] [Google Scholar]
- Wingender E. Compilation of transcription regulating proteins. Nucleic Acids Res. 1988 Mar 25;16(5):1879–1902. doi: 10.1093/nar/16.5.1879. [DOI] [PMC free article] [PubMed] [Google Scholar]