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Blood, 1 June 2006, Vol. 107, No. 11, pp. 4234-4239. Prepublished online as a Blood First Edition Paper on February 7, 2006; DOI 10.1182/blood-2005-08-3343. This Article Full Text Full Text (PDF) All Versions of this Article: 2005-08-3343v1 107/11/4234    most recent 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 Nakata, Y. Articles by Ptasznik, A. Search for Related Content PubMed PubMed Citation Articles by Nakata, Y. Articles by Ptasznik, A. Related Collections Hematopoiesis and Stem Cells Cell Adhesion and Motility Stem Cells in Hematology Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES, CYTOKINES, AND INTERLEUKINS Integrin inhibition through Lyn-dependent cross talk from CXCR4 chemokine receptors in normal human CD34+ marrow cells Yuji Nakata, Brian Tomkowicz, Alan M. Gewirtz, and Andrzej Ptasznik From the Division of Hematology & Oncology, Department of Medicine, University of Pennsylvania School of Medicine, Philadelphia. We studied the effects of Lyn ablation on CXCR4 receptor-mediated migration and adhesion of hematopoietic precursors. Down-regulation of Lyn expression with siRNA greatly reduced CXCR4-dependent hematopoietic cell movement, and increased cell adherence to stroma. This increase was associated with the up-regulated expression of activation-dependent epitopes of the 2 integrin LFA-1 and was prevented by antibodies that selectively block cell adhesion mediated by ICAM-1. Attachment to surfaces coated with ICAM-1 was also enhanced in Lyn-depleted hematopoietic cells, as compared with Lyn-expressing cells. Functional rescue experiments with Lyn siRNA targeting the 3' UTR indicated that the observed effects can be attributed directly to specific inhibition of Lyn. Our results show that in chemokine-stimulated hematopoietic cells Lyn kinase is a positive regulator of cell movement while negatively regulating adhesion to stromal cells by inhibiting the ICAM-1–binding activity of 2 integrins. These results provide a molecular mechanism for cross talk between the chemokine receptor CXCR4 and 2 integrins. This cross talk may allow chemokine receptors to modulate the arrest of rolling hematopoietic precursors on the surface of bone marrow stromal cells. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: P. Banerjee, M. Sieburg, E. Samuelson, and G. Feuer Human T-Cell Lymphotropic Virus Type 1 Infection of CD34+ Hematopoietic Progenitor Cells Induces Cell Cycle Arrest by Modulation of p21cip1/waf1 and Survivin Stem Cells, December 1, 2008; 26(12): 3047 - 3058. [Abstract] [Full Text] [PDF] H. Guan, Z. Zhou, G. E. Gallick, S.-F. Jia, J. Morales, A. K. Sood, S. J. Corey, and E. S. Kleinerman Targeting Lyn inhibits tumor growth and metastasis in Ewing's sarcoma Mol. Cancer Ther., July 1, 2008; 7(7): 1807 - 1816. [Abstract] [Full Text] [PDF] Y.-Y. Chen, M. Malik, B. E. Tomkowicz, R. G. Collman, and A. Ptasznik BCR-ABL1 alters SDF-1{alpha}-mediated adhesive responses through the {beta}2 integrin LFA-1 in leukemia cells Blood, May 15, 2008; 111(10): 5182 - 5186. [Abstract] [Full Text] [PDF] S. Forde, B. J. Tye, S. E. Newey, M. Roubelakis, J. Smythe, C. P. McGuckin, R. Pettengell, and S. M. Watt Endolyn (CD164) modulates the CXCL12-mediated migration of umbilical cord blood CD133+ cells Blood, March 1, 2007; 109(5): 1825 - 1833. [Abstract] [Full Text] [PDF]

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