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Blood, 1 March 2006, Vol. 107, No. 5, pp. 1768-1775. Prepublished online as a Blood First Edition Paper on November 1, 2005; DOI 10.1182/blood-2005-06-2501. This Article Full Text Full Text (PDF) Supplemental Figure All Versions of this Article: 2005-06-2501v1 107/5/1768    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 Kasper, B. Articles by Petersen, F. Search for Related Content PubMed PubMed Citation Articles by Kasper, B. Articles by Petersen, F. Related Collections Hemostasis, Thrombosis, and Vascular Biology Phagocytes Signal Transduction Chemokines, Cytokines, and Interleukins Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  CHEMOKINES, CYTOKINES, AND INTERLEUKINS Neutrophil adhesion to endothelial cells induced by platelet factor 4 requires sequential activation of Ras, Syk, and JNK MAP kinases Brigitte Kasper, Ernst Brandt, Martin Ernst, and Frank Petersen From the Department of Immunology and Cell Biology, Research Center Borstel, Borstel, Germany. Signal transduction mechanisms associated with neutrophil activation by platelet factor 4 (PF4; CXCL4) are as yet poorly characterized. In a recent report, we showed that PF4-induced neutrophil functions (such as adhesion and secondary granule exocytosis) involve the activation of Src-kinases. By analyzing intracellular signals leading to adherence, we here demonstrate by several lines of evidence that in addition to Src-kinases, PF4 signaling involves the monomeric GTPase Ras, the tyrosine kinase Syk, and the MAP kinase JNK. Furthermore, on stimulation, GTPases Rac2 and RhoA were activated, and each was translocated to a different membrane compartment. As shown by inhibitor studies, Rac2 and JNK are located downstream of Syk and Ras. Most intriguingly, the latter 2 elements appear to control the activity of Rac2 and JNK independently of each other at different phases of the activation process. Although a first phase of Rac2 and JNK activation of up to 5 minutes is initiated by Ras, the second phase (5-30 minutes) depends predominantly on the activity of Syk. In summary, we describe that coordinated activity of Syk, Ras, and JNK mediates neutrophil adhesion to endothelial cells and that PF4 induces sequential activation of these elements. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: F. Binet and D. Girard Novel human neutrophil agonistic properties of arsenic trioxide: involvement of p38 mitogen-activated protein kinase and/or c-jun NH2-terminal MAPK but not extracellular signal-regulated kinases-1/2 J. Leukoc. Biol., December 1, 2008; 84(6): 1613 - 1622. [Abstract] [Full Text] [PDF] K. M. Bijli, F. Fazal, M. Minhajuddin, and A. Rahman Activation of Syk by Protein Kinase C-{delta} Regulates Thrombin-induced Intercellular Adhesion Molecule-1 Expression in Endothelial Cells via Tyrosine Phosphorylation of RelA/p65 J. Biol. Chem., May 23, 2008; 283(21): 14674 - 14684. [Abstract] [Full Text] [PDF] B. Kasper, E. Brandt, S. Brandau, and F. Petersen Platelet Factor 4 (CXC Chemokine Ligand 4) Differentially Regulates Respiratory Burst, Survival, and Cytokine Expression of Human Monocytes by Using Distinct Signaling Pathways J. Immunol., August 15, 2007; 179(4): 2584 - 2591. [Abstract] [Full Text] [PDF] S. Struyf, M. D. Burdick, E. Peeters, K. Van den Broeck, C. Dillen, P. Proost, J. Van Damme, and R. M. Strieter Platelet Factor-4 Variant Chemokine CXCL4L1 Inhibits Melanoma and Lung Carcinoma Growth and Metastasis by Preventing Angiogenesis Cancer Res., June 15, 2007; 67(12): 5940 - 5948. [Abstract] [Full Text] [PDF]

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