Abstract
Tip of herpesvirus saimiri associates with Lck and downregulates Lck function in cellular signal transduction. In this report, we demonstrate that mutation of tyrosine 114 of Tip significantly increases Lck-binding activity. This mutant exhibits a dramatic increase in the suppression of cellular tyrosine phosphorylation and surface expression of lymphocyte antigens in comparison with wild-type Tip. In addition, the expression of TipY114 converted the transforming morphology of fibroblasts induced by oncogenic F505 Lck to a normal cellular morphology. These results further support a mechanism by which the association of Tip with Lck negatively regulates Lck-mediated signal transduction.
Full Text
The Full Text of this article is available as a PDF (749.9 KB).
Selected References
These references are in PubMed. This may not be the complete list of references from this article.
- Ahuja S. K., Murphy P. M. Molecular piracy of mammalian interleukin-8 receptor type B by herpesvirus saimiri. J Biol Chem. 1993 Oct 5;268(28):20691–20694. [PubMed] [Google Scholar]
- Albrecht J. C., Nicholas J., Biller D., Cameron K. R., Biesinger B., Newman C., Wittmann S., Craxton M. A., Coleman H., Fleckenstein B. Primary structure of the herpesvirus saimiri genome. J Virol. 1992 Aug;66(8):5047–5058. doi: 10.1128/jvi.66.8.5047-5058.1992. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Albrecht J. C., Nicholas J., Cameron K. R., Newman C., Fleckenstein B., Honess R. W. Herpesvirus saimiri has a gene specifying a homologue of the cellular membrane glycoprotein CD59. Virology. 1992 Sep;190(1):527–530. doi: 10.1016/0042-6822(92)91247-r. [DOI] [PubMed] [Google Scholar]
- Biesinger B., Trimble J. J., Desrosiers R. C., Fleckenstein B. The divergence between two oncogenic Herpesvirus saimiri strains in a genomic region related to the transforming phenotype. Virology. 1990 Jun;176(2):505–514. doi: 10.1016/0042-6822(90)90020-r. [DOI] [PubMed] [Google Scholar]
- Biesinger B., Tsygankov A. Y., Fickenscher H., Emmrich F., Fleckenstein B., Bolen J. B., Bröker B. M. The product of the Herpesvirus saimiri open reading frame 1 (tip) interacts with T cell-specific kinase p56lck in transformed cells. J Biol Chem. 1995 Mar 3;270(9):4729–4734. doi: 10.1074/jbc.270.9.4729. [DOI] [PubMed] [Google Scholar]
- Chang Y., Cesarman E., Pessin M. S., Lee F., Culpepper J., Knowles D. M., Moore P. S. Identification of herpesvirus-like DNA sequences in AIDS-associated Kaposi's sarcoma. Science. 1994 Dec 16;266(5192):1865–1869. doi: 10.1126/science.7997879. [DOI] [PubMed] [Google Scholar]
- Desrosiers R. C., Bakker A., Kamine J., Falk L. A., Hunt R. D., King N. W. A region of the Herpesvirus saimiri genome required for oncogenicity. Science. 1985 Apr 12;228(4696):184–187. doi: 10.1126/science.2983431. [DOI] [PubMed] [Google Scholar]
- Desrosiers R. C., Silva D. P., Waldron L. M., Letvin N. L. Nononcogenic deletion mutants of herpesvirus saimiri are defective for in vitro immortalization. J Virol. 1986 Feb;57(2):701–705. doi: 10.1128/jvi.57.2.701-705.1986. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Du Z., Regier D. A., Desrosiers R. C. Improved recombinant PCR mutagenesis procedure that uses alkaline-denatured plasmid template. Biotechniques. 1995 Mar;18(3):376–378. [PubMed] [Google Scholar]
- Jung J. U., Desrosiers R. C. Association of the viral oncoprotein STP-C488 with cellular ras. Mol Cell Biol. 1995 Dec;15(12):6506–6512. doi: 10.1128/mcb.15.12.6506. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jung J. U., Desrosiers R. C. Distinct functional domains of STP-C488 of herpesvirus saimiri. Virology. 1994 Nov 1;204(2):751–758. doi: 10.1006/viro.1994.1590. [DOI] [PubMed] [Google Scholar]
- Jung J. U., Lang S. M., Friedrich U., Jun T., Roberts T. M., Desrosiers R. C., Biesinger B. Identification of Lck-binding elements in tip of herpesvirus saimiri. J Biol Chem. 1995 Sep 1;270(35):20660–20667. doi: 10.1074/jbc.270.35.20660. [DOI] [PubMed] [Google Scholar]
- Jung J. U., Lang S. M., Jun T., Roberts T. M., Veillette A., Desrosiers R. C. Downregulation of Lck-mediated signal transduction by tip of herpesvirus saimiri. J Virol. 1995 Dec;69(12):7814–7822. doi: 10.1128/jvi.69.12.7814-7822.1995. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jung J. U., Stäger M., Desrosiers R. C. Virus-encoded cyclin. Mol Cell Biol. 1994 Nov;14(11):7235–7244. doi: 10.1128/mcb.14.11.7235. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Jung J. U., Trimble J. J., King N. W., Biesinger B., Fleckenstein B. W., Desrosiers R. C. Identification of transforming genes of subgroup A and C strains of Herpesvirus saimiri. Proc Natl Acad Sci U S A. 1991 Aug 15;88(16):7051–7055. doi: 10.1073/pnas.88.16.7051. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Lund T., Medveczky M. M., Medveczky P. G. Herpesvirus saimiri Tip-484 membrane protein markedly increases p56lck activity in T cells. J Virol. 1997 Jan;71(1):378–382. doi: 10.1128/jvi.71.1.378-382.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller C. L., Burkhardt A. L., Lee J. H., Stealey B., Longnecker R., Bolen J. B., Kieff E. Integral membrane protein 2 of Epstein-Barr virus regulates reactivation from latency through dominant negative effects on protein-tyrosine kinases. Immunity. 1995 Feb;2(2):155–166. doi: 10.1016/s1074-7613(95)80040-9. [DOI] [PubMed] [Google Scholar]
- Miller C. L., Lee J. H., Kieff E., Longnecker R. An integral membrane protein (LMP2) blocks reactivation of Epstein-Barr virus from latency following surface immunoglobulin crosslinking. Proc Natl Acad Sci U S A. 1994 Jan 18;91(2):772–776. doi: 10.1073/pnas.91.2.772. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Miller C. L., Longnecker R., Kieff E. Epstein-Barr virus latent membrane protein 2A blocks calcium mobilization in B lymphocytes. J Virol. 1993 Jun;67(6):3087–3094. doi: 10.1128/jvi.67.6.3087-3094.1993. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nava V. E., Cheng E. H., Veliuona M., Zou S., Clem R. J., Mayer M. L., Hardwick J. M. Herpesvirus saimiri encodes a functional homolog of the human bcl-2 oncogene. J Virol. 1997 May;71(5):4118–4122. doi: 10.1128/jvi.71.5.4118-4122.1997. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Nicholas J., Cameron K. R., Honess R. W. Herpesvirus saimiri encodes homologues of G protein-coupled receptors and cyclins. Nature. 1992 Jan 23;355(6358):362–365. doi: 10.1038/355362a0. [DOI] [PubMed] [Google Scholar]
- Rother R. P., Rollins S. A., Fodor W. L., Albrecht J. C., Setter E., Fleckenstein B., Squinto S. P. Inhibition of complement-mediated cytolysis by the terminal complement inhibitor of herpesvirus saimiri. J Virol. 1994 Feb;68(2):730–737. doi: 10.1128/jvi.68.2.730-737.1994. [DOI] [PMC free article] [PubMed] [Google Scholar]
- Straus D. B., Weiss A. Genetic evidence for the involvement of the lck tyrosine kinase in signal transduction through the T cell antigen receptor. Cell. 1992 Aug 21;70(4):585–593. doi: 10.1016/0092-8674(92)90428-f. [DOI] [PubMed] [Google Scholar]
- Thomson B. J., Nicholas J. Superantigen function. Nature. 1991 Jun 13;351(6327):530–530. doi: 10.1038/351530a0. [DOI] [PubMed] [Google Scholar]
- Veillette A., Caron L., Fournel M., Pawson T. Regulation of the enzymatic function of the lymphocyte-specific tyrosine protein kinase p56lck by the non-catalytic SH2 and SH3 domains. Oncogene. 1992 May;7(5):971–980. [PubMed] [Google Scholar]
- Wiese N., Tsygankov A. Y., Klauenberg U., Bolen J. B., Fleischer B., Bröker B. M. Selective activation of T cell kinase p56lck by Herpesvirus saimiri protein tip. J Biol Chem. 1996 Jan 12;271(2):847–852. doi: 10.1074/jbc.271.2.847. [DOI] [PubMed] [Google Scholar]
- Yao Z., Fanslow W. C., Seldin M. F., Rousseau A. M., Painter S. L., Comeau M. R., Cohen J. I., Spriggs M. K. Herpesvirus Saimiri encodes a new cytokine, IL-17, which binds to a novel cytokine receptor. Immunity. 1995 Dec;3(6):811–821. doi: 10.1016/1074-7613(95)90070-5. [DOI] [PubMed] [Google Scholar]
- Yao Z., Maraskovsky E., Spriggs M. K., Cohen J. I., Armitage R. J., Alderson M. R. Herpesvirus saimiri open reading frame 14, a protein encoded by T lymphotropic herpesvirus, binds to MHC class II molecules and stimulates T cell proliferation. J Immunol. 1996 May 1;156(9):3260–3266. [PubMed] [Google Scholar]
- Yoon D. W., Lee H., Seol W., DeMaria M., Rosenzweig M., Jung J. U. Tap: a novel cellular protein that interacts with tip of herpesvirus saimiri and induces lymphocyte aggregation. Immunity. 1997 May;6(5):571–582. doi: 10.1016/s1074-7613(00)80345-3. [DOI] [PubMed] [Google Scholar]