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Blood, 1 December 2006, Vol. 108, No. 12, pp. 3919-3927. Prepublished online as a Blood First Edition Paper on August 1, 2006; DOI 10.1182/blood-2005-12-030387. This Article Full Text (PDF) Supplemental Videos and Figures All Versions of this Article: blood-2005-12-030387v1 108/12/3919    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 Schymeinsky, J. Articles by Walzog, B. Search for Related Content PubMed PubMed Citation Articles by Schymeinsky, J. Articles by Walzog, B. Social Bookmarking                   What's this?  Previous Article  |  Next Article  Submitted December 22, 2005 Accepted July 12, 2006 The Vav binding site of the non-receptor tyrosine kinase Syk at Tyr 348 is critical for 2 integrin (CD11/CD18)-mediated neutrophil migration Jurgen Schymeinsky, Anca Sindrilaru, David Frommhold, Markus Sperandio, Ronald Gerstl, Cornelia Then, Attila Mocsai, Karin Scharffetter-Kochanek, and Barbara Walzog* Dept. of Physiology, Ludwig-Maximilians-University Munich, Munich, Germany Dept. of Dermatology and Allergic Diseases, University of Ulm, Ulm, Germany Dept. of Pediatrics, Neonatal Unit, University of Heidelberg, Heidelberg, Germany Dept. of Physiology, Semmelweis University School of Medicine, Budapest, Hungary * Corresponding author; email: walzog{at}lrz.uni-muenchen.de. Leukocyte adhesion via 2 integrins (CD11/CD18) activates the tyrosine kinase Syk. We found that Syk was enriched at the lamellipodium during N-formyl-Met-Leu-Phe-induced migration of neutrophil-like differentiated HL-60 cells. Here, Syk co-localized with Vav, a guanine nucleotide exchange factor for Rac and Cdc42. The enrichment of Syk at the lamellipodium and its co-localization with Vav were absent upon expression of a Syk kinase dead mutant (Syk K402R) or a Syk mutant lacking the binding site of Vav (Syk Y348F). Live cell imaging revealed that both mutations resulted in excessive lamellipodium formation and severely compromised migration compared to control cells. Similar results were obtained upon downregulation of Syk by RNAi technique as well as in Syk-/- neutrophils from wildtype mice reconstituted with Syk-/- bone marrow. A pivotal role of Syk in vivo was demonstrated in the Arthus reaction where neutrophil extravasation, edema formation and hemorrhage were profoundly diminished in Syk-/- bone marrow chimeras compared to control animals. In the inflamed cremaster muscle, Syk-/- neutrophils revealed a defect in adhesion and migration. These findings indicate that Syk is critical for 2 integrin-mediated neutrophil migration in vitro and plays a fundamental role for neutrophil recruitment during the inflammatory response in vivo. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: J. Schymeinsky, R. Gerstl, I. Mannigel, K. Niedung, D. Frommhold, K. Panthel, J. Heesemann, M. Sixt, T. Quast, W. Kolanus, et al. A fundamental role of mAbp1 in neutrophils: impact on {beta}2 integrin-mediated phagocytosis and adhesion in vivo Blood, November 5, 2009; 114(19): 4209 - 4220. [Abstract] [Full Text] [PDF] F. Wang The Signaling Mechanisms Underlying Cell Polarity and Chemotaxis Cold Spring Harb Perspect Biol, October 1, 2009; 1(4): a002980 - a002980. [Abstract] [Full Text] [PDF] M. Phillipson, B. Heit, S. A. Parsons, B. Petri, S. C. Mullaly, P. Colarusso, R. M. Gower, G. Neely, S. I. Simon, and P. Kubes Vav1 Is Essential for Mechanotactic Crawling and Migration of Neutrophils out of the Inflamed Microvasculature J. Immunol., June 1, 2009; 182(11): 6870 - 6878. [Abstract] [Full Text] [PDF] X. Zhang, U. Shrikhande, B. M. Alicie, Q. Zhou, and R. L. Geahlen Role of the Protein Tyrosine Kinase Syk in Regulating Cell-Cell Adhesion and Motility in Breast Cancer Cells Mol. Cancer Res., May 1, 2009; 7(5): 634 - 644. [Abstract] [Full Text] [PDF] Z. Jakus, E. Simon, D. Frommhold, M. Sperandio, and A. Mocsai Critical role of phospholipase C{gamma}2 in integrin and Fc receptor-mediated neutrophil functions and the effector phase of autoimmune arthritis J. Exp. Med., March 16, 2009; 206(3): 577 - 593. [Abstract] [Full Text] [PDF] Y. Tohyama and H. Yamamura Protein Tyrosine Kinase, Syk: A Key Player in Phagocytic Cells J. Biochem., March 1, 2009; 145(3): 267 - 273. [Abstract] [Full Text] [PDF] A. Utomo, J. Hirahashi, D. Mekala, K. 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