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Blood, 15 May 2005, Vol. 105, No. 10, pp. 3987-3994. Prepublished online as a Blood First Edition Paper on January 21, 2005; DOI 10.1182/blood-2004-07-2781. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-07-2781v1 105/10/3987    most recent Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Prakash, O. Articles by Samaniego, F. Search for Related Content PubMed PubMed Citation Articles by Prakash, O. Articles by Samaniego, F. Related Collections Hemostasis, Thrombosis, and Vascular Biology Neoplasia Oncogenes and Tumor Suppressors Signal Transduction Related Article in Blood Online Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  NEOPLASIA Activation of Src kinase Lyn by the Kaposi sarcoma–associated herpesvirus K1 protein: implications for lymphomagenesis Om Prakash, O. Rama Swamy, Xiochang Peng, Zhen-Ya Tang, Li Li, Janet E. Larson, J. Craig Cohen, Javed Gill, Gist Farr, Suizhao Wang, and Felipe Samaniego From the Laboratory of Molecular Oncology and the Department of Pathology, Ochsner Clinic Foundation, New Orleans, LA; the Department of Lymphoma/Myeloma and Immunology, The University of Texas M. D. Anderson Cancer Center, and the Program in Gene Therapy and Virology, The University of Texas Graduate School of Biomedical Sciences at Houston, TX. The K1 gene of Kaposi sarcoma–associated herpesvirus (KSHV) encodes a transmembrane glycoprotein bearing a functional immunoreceptor tyrosine-based activation motif (ITAM). Previously, we reported that the K1 protein induced plasmablastic lymphomas in K1 transgenic mice, and that these lymphomas showed enhanced Lyn kinase activity. Here, we report that systemic administration of the nuclear factor kappa B (NF-B) inhibitor Bay 11-7085 or an anti–vascular endothelial growth factor (VEGF) antibody significantly reduced K1 lymphoma growth in nude mice. Furthermore, in KVL-1 cells, a cell line derived from a K1 lymphoma, inhibition of Lyn kinase activity by the Src kinase inhibitor PP2 decreased VEGF induction, NF-B activity, and the cell proliferation index by 50% to 75%. In contrast, human B-cell lymphoma BJAB cells expressing K1, but not the ITAM sequence–deleted mutant K1, showed a marked increase in Lyn kinase activity with concomitant VEGF induction and NF-B activation, indicating that ITAM sequences were required for the Lyn kinase–mediated activation of these factors. Our results suggested that K1-mediated constitutive Lyn kinase activation in K1 lymphoma cells is crucial for the production of VEGF and NF-B activation, both strongly implicated in the development of KSHV-induced lymphoproliferative disorders. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? Related Article in Blood Online: Kinase Lynks to herpesvirus lymphomagenesis Christopher H. Parsons Blood 2005 105: 3762. [Full Text] [PDF] This article has been cited by other articles: Y. Izumiya, C. Izumiya, D. Hsia, T. J. Ellison, P. A. Luciw, and H.-J. 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[Abstract] [Full Text] [PDF] H. Guan, Z. Zhou, G. E. Gallick, S.-F. Jia, J. Morales, A. K. Sood, S. J. Corey, and E. S. Kleinerman Targeting Lyn inhibits tumor growth and metastasis in Ewing's sarcoma Mol. Cancer Ther., July 1, 2008; 7(7): 1807 - 1816. [Abstract] [Full Text] [PDF] S. Tauzin, H. Ding, K. Khatib, I. Ahmad, D. Burdevet, G. van Echten-Deckert, J. A. Lindquist, B. Schraven, N.-u. Din, B. Borisch, et al. Oncogenic association of the Cbp/PAG adaptor protein with the Lyn tyrosine kinase in human B-NHL rafts Blood, February 15, 2008; 111(4): 2310 - 2320. [Abstract] [Full Text] [PDF] S. Wang, S. Wang, H. Maeng, D. P. Young, O. Prakash, L. E. Fayad, A. Younes, and F. Samaniego K1 protein of human herpesvirus 8 suppresses lymphoma cell Fas-mediated apoptosis Blood, March 1, 2007; 109(5): 2174 - 2182. [Abstract] [Full Text] [PDF] G. Kroemer, L. Galluzzi, and C. Brenner Mitochondrial Membrane Permeabilization in Cell Death Physiol Rev, January 1, 2007; 87(1): 99 - 163. 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