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Blood, 1 April 2005, Vol. 105, No. 7, pp. 2869-2876. Prepublished online as a Blood First Edition Paper on December 7, 2004; DOI 10.1182/blood-2004-08-2981. This Article Full Text (PDF) All Versions of this Article: 2004-08-2981v1 105/7/2869    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 Aasheim, H.-C. Articles by Finne, E. F Search for Related Content PubMed PubMed Citation Articles by Aasheim, H.-C. Articles by Finne, E. F Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted August 2, 2004 Accepted November 30, 2004 Ephrin-A1 binding to CD4+ T lymphocytes stimulates migration and induces tyrosine phosphorylation of PYK2 Hans-Christian Aasheim*, Jan Delabie, and Eivind F Finne Department of Immunology, The Norwegian Radium Hospital, Oslo, Norway Department of Pathology, The Norwegian Radium Hospital, Oslo, Norway * Corresponding author; email: h.c.asheim{at}labmed.uio.no. Eph receptors, the largest subfamily of receptor tyrosine kinases, and their ephrin ligands are important mediators of cell-cell communication regulating cell attachment, shape and mobility. Here we demonstrate that CD4+ T lymphocytes express the EphA1 and EphA4 receptors, and that these cells bind the ligand ephrin-A1. Further we show ephrin-A1 expression in vivo on high endothelial venules (HEV) endothelial cells. Ephrin-A1 binding to CD4+ T cells stimulates both SDF-1 and MIP3 mediated chemotaxis. In line with the increased chemotactic response, increased actin polymerization is observed in particular with the combination of ephrin-A1 and SDF-1. Signaling through EphA receptors induces intracellular tyrosine phosphorylation. In particular PYK2 is phosphorylated on tyrosine residues 402 and 580. Ephrin-A1-induced chemotaxis and intracellular tyrosine phosphorylation, including EphA1 and Pyk2, was inhibited by Tyrphostin-A9. In conclusion, ligand engagement of EphA receptors on CD4+ T cells stimulates chemotaxis, induces intracellular tyrosine phosphorylation and affects actin polymerization. This, together with our finding that ephrin-A1 is expressed by HEV, suggests a role for Eph receptors in transendothelial migration. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: A. R. Anand, A. Prasad, R. R. Bradley, Y. S. Deol, T. Nagaraja, X. Ren, E. F. Terwilliger, and R. K. Ganju HIV-1 gp120-induced migration of dendritic cells is regulated by a novel kinase cascade involving Pyk2, p38 MAP kinase, and LSP1 Blood, October 22, 2009; 114(17): 3588 - 3600. [Abstract] [Full Text] [PDF] E. V. Bocharov, M. L. Mayzel, P. E. Volynsky, M. V. Goncharuk, Y. S. Ermolyuk, A. A. Schulga, E. O. Artemenko, R. G. Efremov, and A. S. Arseniev Spatial Structure and pH-dependent Conformational Diversity of Dimeric Transmembrane Domain of the Receptor Tyrosine Kinase EphA1 J. Biol. Chem., October 24, 2008; 283(43): 29385 - 29395. [Abstract] [Full Text] [PDF] H. L. Holen, M. Shadidi, K. Narvhus, O. Kjosnes, A. Tierens, and H.-C. Aasheim Signaling through ephrin-A ligand leads to activation of Src-family kinases, Akt phosphorylation, and inhibition of antigen receptor-induced apoptosis J. Leukoc. Biol., October 1, 2008; 84(4): 1183 - 1191. [Abstract] [Full Text] [PDF] S. H. Wimmer-Kleikamp, E. Nievergall, K. Gegenbauer, S. Adikari, M. Mansour, T. Yeadon, A. W. Boyd, N. R. Patani, and M. Lackmann Elevated protein tyrosine phosphatase activity provokes Eph/ephrin-facilitated adhesion of pre-B leukemia cells Blood, August 1, 2008; 112(3): 721 - 732. [Abstract] [Full Text] [PDF] G. Jiang, T. Freywald, J. Webster, D. Kozan, R. Geyer, J. DeCoteau, A. Narendran, and A. Freywald In Human Leukemia Cells Ephrin-B-Induced Invasive Activity Is Supported by Lck and Is Associated with Reassembling of Lipid Raft Signaling Complexes Mol. Cancer Res., February 1, 2008; 6(2): 291 - 305. [Abstract] [Full Text] [PDF] T. Kitamura, Y. Kabuyama, A. Kamataki, M. K. Homma, H. Kobayashi, S. Aota, S.-i. Kikuchi, and Y. Homma Enhancement of lymphocyte migration and cytokine production by ephrinB1 system in rheumatoid arthritis Am J Physiol Cell Physiol, January 1, 2008; 294(1): C189 - C196. [Abstract] [Full Text] [PDF] D. Pfaff, U. Fiedler, and H. G. Augustin Emerging roles of the Angiopoietin-Tie and the ephrin-Eph systems as regulators of cell trafficking J. Leukoc. Biol., October 1, 2006; 80(4): 719 - 726. [Abstract] [Full Text] [PDF] T. Korff, G. Dandekar, D. Pfaff, T. Fuller, W. Goettsch, H. Morawietz, F. Schaffner, and H. G. Augustin Endothelial EphrinB2 Is Controlled by Microenvironmental Determinants and Associates Context-Dependently With CD31 Arterioscler Thromb Vasc Biol, March 1, 2006; 26(3): 468 - 474. [Abstract] [Full Text] [PDF]

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