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Blood, 15 May 2006, Vol. 107, No. 10, pp. 3821-3831. Prepublished online as a Blood First Edition Paper on December 20, 2005; DOI 10.1182/blood-2004-01-0214. This Article Full Text (PDF) Supplemental Videos All Versions of this Article: 2004-01-0214v1 107/10/3821    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 Dagan-Berger, M. Articles by Peled, A. Search for Related Content PubMed PubMed Citation Articles by Dagan-Berger, M. Articles by Peled, A. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted January 20, 2004 Accepted October 18, 2005 Role of CXCR3 carboxyl-terminus and third intracellular loop in receptor-mediated migration, adhesion and internalization in response to CXCL11 Michal Dagan-Berger, Rotem Feniger-Barish, Shani Avniel, Hanna Wald, Eithan Galun, Valentin Grabovsky, Ronen Alon, Arnon Nagler, Adit Ben-Baruch, and Amnon Peled* The Institute of Gene Therapy, Hadassah University Hospital, Jerusalem, Israel Department of Immunology, Weizmann Institute of Science, Rehovot,, Israel Dep. Of BM Transplantation, Chaim Sheba Medical Center, Tel Hashomer, Israel Department of Cell Research and Immunology, Tel-Aviv University, Tel-Aviv, Israel * Corresponding author; email: peled{at}hadassah.org.il. The chemokine receptor CXCR3 is predominantly expressed on activated T and NK cells. CXCR3 and its ligands, CXCL11, CXCL10 and CXCL9, play a major role in Th1-dependent inflammatory responses. CXCL11 is the most dominant physiological inducer of adhesion, migration and internalization of CXCR3. To study the role of CXCR3 carboxyl-terminus and the third intracellular loop (3i) in chemokine-mediated migration, adhesion and CXCR3 internalization, we generated CXCR3 receptors mutated in their distal (Ser-Thr domain) or proximal (trileucine domain) membrane carboxyl terminus, and/or the third intracellular loop. We found that migration of CXCR3-expressing HEK 293 cells toward CXCL11 was pertussis toxin-dependent and required the membrane proximal carboxyl terminus of CXCR3. Internalization induced by CXCL11 and PKC activation was also regulated by the membrane proximal carboxyl terminus; however, only CXCL11, induced internalization required the LLL motif of this region. Internalization and Ca2+ flux induced by CXCL11 were independent of the 3i loop S245, whereas, migration at high CXCL11 concentrations, integrin-dependent adhesion and actin polymerization were S245-dependent. Our findings indicate that CXCL11-dependent CXCR3 internalization and cell migration are regulated by the CXCR3 membrane proximal carboxyl terminus, whereas adhesion is regulated by the 3i loop S245. Thus, distinct conformational changes induced by a given CXCR3 ligand trigger different downstream effectors of adhesion, motility and CXCR3 desensitization. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: S. Cepok, H. Schreiber, S. Hoffmann, D. Zhou, O. Neuhaus, G. von Geldern, S. Hochgesand, S. Nessler, V. Rothhammer, M. Lang, et al. Enhancement of Chemokine Expression by Interferon Beta Therapy in Patients With Multiple Sclerosis Arch Neurol, October 1, 2009; 66(10): 1216 - 1223. [Abstract] [Full Text] [PDF] S. He, Q. Cao, Y. Qiu, J. Mi, J. Z. Zhang, M. Jin, H. Ge, S. G. Emerson, Y. Zhang, and Y. Zhang A New Approach to the Blocking of Alloreactive T Cell-Mediated Graft-versus-Host Disease by In Vivo Administration of Anti-CXCR3 Neutralizing Antibody J. Immunol., December 1, 2008; 181(11): 7581 - 7592. [Abstract] [Full Text] [PDF] T. R. Wuest and D. J. J. Carr Dysregulation of CXCR3 Signaling due to CXCL10 Deficiency Impairs the Antiviral Response to Herpes Simplex Virus 1 Infection J. Immunol., December 1, 2008; 181(11): 7985 - 7993. [Abstract] [Full Text] [PDF] C. Otero, P. S. Eisele, K. Schaeuble, M. Groettrup, and D. F. Legler Distinct motifs in the chemokine receptor CCR7 regulate signal transduction, receptor trafficking and chemotaxis J. Cell Sci., August 15, 2008; 121(16): 2759 - 2767. [Abstract] [Full Text] [PDF] A. Meiser, A. Mueller, E. L. Wise, E. M. McDonagh, S. J. Petit, N. Saran, P. C. Clark, T. J. Williams, and J. E. Pease The Chemokine Receptor CXCR3 Is Degraded following Internalization and Is Replenished at the Cell Surface by De Novo Synthesis of Receptor J. Immunol., May 15, 2008; 180(10): 6713 - 6724. [Abstract] [Full Text] [PDF]

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