QUICK SEARCH:   [advanced] Author: Keyword(s):
Home     Help     Feedback     Subscriptions     Archive     Search     Table of Contents

First published online 16 August 2005
doi: 10.1242/jcs.02518

This Article Figures Only Full Text Full Text (PDF) All Versions of this Article: jcs.02518v1 118/17/3949    most recent Alert me when this article is cited Alert me if a correction is posted 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Urbinati, C. Articles by Rusnati, M. Search for Related Content PubMed PubMed Citation Articles by Urbinati, C. Articles by Rusnati, M. Pubmed/NCBI databases Gene GEO Profiles HomoloGene UniGene Substance via MeSH Social Bookmarking                         What's this?

_vß₃-integrin-dependent activation of focal adhesion kinase mediates NF-B activation and motogenic activity by HIV-1 Tat in endothelial cells

¹ General Pathology and Immunology, Department of Biomedical Sciences and Biotechnology, School of Medicine, University of Brescia, viale Europe 11, 25123 Brescia, Italy
² International Center for Genetic Engineering and Biotechnology, Padriciano 99, 34012 Trieste, Italy
³ The Scripps Research Institute, Department of Immunology, 10550 North Torrey Pines Road, La Jolla, CA 92037, USA

^* Author for correspondence (e-mail: rusnati{at}med.unibs.it)

Accepted 3 June 2005

Once in the extracellular environment, the transactivator protein HIV-1 Tat exerts several pleiotropic effects by interacting with different cellular receptors, including integrin _vß₃. Real-time surface plasmon resonance analysis reveals that Tat/_Vß₃ interaction occurs with rapid kinetics (association and dissociation rates equal to 1.16x10⁷ M^-1 s^-1 and 3.78x10^-1 s^-1, respectively) and high affinity (dissociation constant = 32 nM). Through this interaction, substratum-immobilized Tat promotes adhesion and motogenic activity in endothelial cells. Also, _vß₃/Tat interaction triggers the activation of focal adhesion kinase, RhoA and pp60^src. Overexpression of the dominant negative form of focal adhesion kinase, but not of an inactive Leu₁₀₃₄Ser substitution mutant isoform, impairs the activation of focal adhesion kinase and RhoA, but not that of pp60^src, without affecting endothelial cell adhesion and spreading. _vß₃/Tat interaction triggers the activation of NF-B in endothelial cells in a focal adhesion kinase-, RhoA- and pp60^src-dependent manner, as shown in dominant negative focal adhesion kinase transfectants or using specific pharmacological inhibitors. Finally, the activation of focal adhesion kinase, RhoA, NF-B and pp60^src are required to mediate the motogenic activity of Tat in endothelial cells.

Since Tat accumulates in an immobilized form in the extracellular matrix, these results provide new biochemical and biological insights about _vß₃/Tat interaction exploitable for the design of anti-Tat strategies.

Key words: HIV-1 Tat, _vß₃ integrin, endothelium, FAK, NF-B

CiteULike    Complore    Connotea    Del.icio.us    Digg    Reddit    Technorati    Twitter    What's this?

This article has been cited by other articles:

				C. Urbinati, S. Nicoli, M. Giacca, G. David, S. Fiorentini, A. Caruso, M. Alfano, L. Cassetta, M. Presta, and M. Rusnati HIV-1 Tat and heparan sulfate proteoglycan interaction: a novel mechanism of lymphocyte adhesion and migration across the endothelium Blood, October 8, 2009; 114(15): 3335 - 3342. [Abstract] [Full Text] [PDF]

				R. F. Wu, Z. Ma, D. P. Myers, and L. S. Terada HIV-1 Tat Activates Dual Nox Pathways Leading to Independent Activation of ERK and JNK MAP Kinases J. Biol. Chem., December 28, 2007; 282(52): 37412 - 37419. [Abstract] [Full Text] [PDF]

				A. Bugatti, C. Urbinati, C. Ravelli, E. De Clercq, S. Liekens, and M. Rusnati Heparin-Mimicking Sulfonic Acid Polymers as Multitarget Inhibitors of Human Immunodeficiency Virus Type 1 Tat and gp120 Proteins Antimicrob. Agents Chemother., July 1, 2007; 51(7): 2337 - 2345. [Abstract] [Full Text] [PDF]

				C. Urbinati, S. Mitola, E. Tanghetti, C. Kumar, J. Waltenberger, D. Ribatti, M. Presta, and M. Rusnati Integrin {alpha}V{beta}3 as a Target for Blocking HIV-1 Tat-Induced Endothelial Cell Activation In Vitro and Angiogenesis In Vivo Arterioscler Thromb Vasc Biol, November 1, 2005; 25(11): 2315 - 2320. [Abstract] [Full Text] [PDF]