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This Article Full Text Full Text (PDF) 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 Nicot, C. Articles by Franchini, G. Search for Related Content PubMed PubMed Citation Articles by Nicot, C. Articles by Franchini, G. Related Collections Neoplasia Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  Blood, 1 August 2001, Vol. 98, No. 3, pp. 823-829 NEOPLASIA HTLV-1 p12I protein enhances STAT5 activation and decreases the interleukin-2 requirement for proliferation of primary human peripheral blood mononuclear cells Christophe Nicot, James C. Mulloy, Maria G. Ferrari, Julie M. Johnson, Kaisong Fu, Risaku Fukumoto, Raffaella Trovato, Jake Fullen, Warren J. Leonard, and Genoveffa Franchini From the National Cancer Institute, Basic Research Laboratory, Bethesda, MD; and the National Heart, Lung, and Blood Institute, Laboratory of Molecular Immunology, Bethesda, MD. The p12I protein, encoded by the pX open reading frame I of the human T-lymphotropic virus type 1 (HTLV-1), is a hydrophobic protein that localizes to the endoplasmic reticulum and the Golgi. Although p12I contains 4 minimal proline-rich, src homology 3-binding motifs (PXXP), a characteristic commonly found in proteins involved in signaling pathways, it has not been known whether p12I has a role in modulating intracellular signaling pathways. This study demonstrated that p12I binds to the cytoplasmic domain of the interleukin-2 receptor (IL-2R)  chain that is involved in the recruitment of the Jak1 and Jak3 kinases. As a result of this interaction, p12I increases signal transducers and activators of transcription 5 (STAT5) DNA binding and transcriptional activity and this effect depends on the presence of both IL-2R  and c chains and Jak3. Transduction of primary human peripheral blood mononuclear cells (PBMCs) with a human immunodeficiency virus type 1-based retroviral vector expressing p12I also resulted in increased STAT5 phosphorylation and DNA binding. However, p12I could increase proliferation of human PBMCs only after stimulation of T-cell receptors by treatment of cells with low concentrations of CD3 and CD28 antibodies. In addition, the proliferative advantage of p12I-transduced PBMCs was evident mainly at low concentrations of IL-2. Together, these data indicate that p12I may confer a proliferative advantage on HTLV-1-infected cells in the presence of suboptimal antigen stimulation and that this event may account for the clonal proliferation of infected T cells in vivo. © 2001 by The American Society of Hematology.   CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: R. Fukumoto, V. Andresen, I. Bialuk, V. Cecchinato, J.-C. Walser, V. W. Valeri, J. M. Nauroth, A. Gessain, C. Nicot, and G. Franchini In vivo genetic mutations define predominant functions of the human T-cell leukemia/lymphoma virus p12I protein Blood, April 16, 2009; 113(16): 3726 - 3734. [Abstract] [Full Text] [PDF] M. Li, M. Kesic, H. Yin, L. Yu, and P. L. Green Kinetic Analysis of Human T-Cell Leukemia Virus Type 1 Gene Expression in Cell Culture and Infected Animals J. Virol., April 15, 2009; 83(8): 3788 - 3797. [Abstract] [Full Text] [PDF] C. Grant, U. Oh, K. 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	Copyright © 2001 by American Society of Hematology         Online ISSN: 1528-0020