SEARCH:   Advanced

Blood, 15 May 2008, Vol. 111, No. 10, pp. 4892-4901. Prepublished online as a Blood First Edition Paper on March 12, 2008; DOI 10.1182/blood-2007-11-125039. This Article Full Text (PDF) Supplemental Figures All Versions of this Article: blood-2007-11-125039v1 111/10/4892    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 Rights and Permissions Citing Articles Citing Articles via HighWire Citing Articles via CrossRef Citing Articles via Google Scholar Google Scholar Articles by Murooka, T. T Articles by Fish, E. N Search for Related Content PubMed PubMed Citation Articles by Murooka, T. T Articles by Fish, E. N Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted November 26, 2007 Accepted February 20, 2008 CCL5-mediated T cell chemotaxis involves the initiation of mRNA translation through mTOR/4E-BP1 Thomas T Murooka, Ramtin Rahbar, Leonidas C Platanias, and Eleanor N Fish* Division of Cellular and Molecular Biology, Toronto General Research Institute, UHN & Department of Immunology, University of Toronto, Toronto, Canada Division of Hematology/Oncology, Robert H. Lurie Comprehensive Cancer Center, Northwestern University Medical School, Chicago, IL, United States * Corresponding author; email: en.fish{at}utoronto.ca. The multi-step, coordinated process of T cell chemotaxis requires chemokines, and their chemokine receptors, to invoke signaling events to direct cell migration. Here, we examined the role for CCL5-mediated initiation of mRNA translation in CD4+ T cell chemotaxis. Using rapamycin, an inhibitor of mTOR, our data show the importance of mTOR in CCL5-mediated T cell migration. Cycloheximide, but not actinomycin D, significantly reduced chemotaxis, suggesting a possible role for mRNA translation in T cell migration. CCL5 induced phosphorylation/activation of mTOR, p70 S6K1 and ribosomal protein S6. Additionally, CCL5 induced PI-3'K-, phospholipase D (PLD)- and mTOR-dependent phosphorylation and deactivation of the transcriptional repressor 4E-BP1, which resulted in its dissociation from the eukaryotic initiation factor-4E (eIF4E). Subsequently, eIF4E associated with scaffold protein eIF4G, forming the eIF4F translation initiation complex. Indeed, CCL5 initiated active translation of mRNA, shown by the increased presence of high-molecular-weight polysomes which were significantly reduced by rapamycin treatment. Notably, CCL5 induced protein translation of cyclin D1 and MMP-9, known mediators of migration. Taken together, we describe a novel mechanism by which CCL5 influences translation of rapamycin-sensitive mRNAs and "primes" CD4+ T cell for efficient chemotaxis. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: D. J. Pappas, G. Coppola, P. A. Gabatto, F. Gao, D. H. Geschwind, J. R. Oksenberg, and S. E. Baranzini Longitudinal system-based analysis of transcriptional responses to type I interferons Physiol Genomics, August 7, 2009; 38(3): 362 - 371. [Abstract] [Full Text] [PDF] R. Baetta, A. Granata, M. Canavesi, N. Ferri, L. Arnaboldi, S. Bellosta, P. Pfister, and A. Corsini Everolimus Inhibits Monocyte/Macrophage Migration in Vitro and Their Accumulation in Carotid Lesions of Cholesterol-Fed Rabbits J. Pharmacol. Exp. Ther., February 1, 2009; 328(2): 419 - 425. [Abstract] [Full Text] [PDF] J. B.K. Schwarz, N. Langwieser, N. N. Langwieser, M. J. Bek, S. Seidl, H.-H. Eckstein, B. Lu, A. Schomig, H. Pavenstadt, and D. Zohlnhofer Novel Role of the CXC Chemokine Receptor 3 in Inflammatory Response to Arterial Injury: Involvement of mTORC1 Circ. Res., January 30, 2009; 104(2): 189 - 200. [Abstract] [Full Text] [PDF]

	Copyright © 2008 by American Society of Hematology         Online ISSN: 1528-0020