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Blood, 1 May 2005, Vol. 105, No. 9, pp. 3561-3568. Prepublished online as a Blood First Edition Paper on January 6, 2005; DOI 10.1182/blood-2004-10-4089. This Article Full Text Full Text (PDF) All Versions of this Article: 2004-10-4089v1 105/9/3561    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 Belkin, A. M. Articles by Medved, L. Search for Related Content PubMed PubMed Citation Articles by Belkin, A. M. Articles by Medved, L. Related Collections Hemostasis, Thrombosis, and Vascular Biology Cell Adhesion and Motility Signal Transduction Social Bookmarking                   What's this?  Previous Article  |  Table of Contents  |  Next Article  HEMOSTASIS, THROMBOSIS, AND VASCULAR BIOLOGY Transglutaminase-mediated oligomerization of the fibrin(ogen) C domains promotes integrin-dependent cell adhesion and signaling Alexey M. Belkin, Galina Tsurupa, Evgeny Zemskov, Yuri Veklich, John W. Weisel, and Leonid Medved From the Department of Biochemistry and Molecular Biology and Greenebaum Cancer Center, University of Maryland School of Medicine, Baltimore; and the Department of Cell and Developmental Biology, University of Pennsylvania School of Medicine, Philadelphia. Interactions of endothelial cells with fibrin(ogen) are implicated in inflammation, angiogenesis, and wound healing. Cross-linking of the fibrinogen C domains with factor XIIIa generates ordered C oligomers mimicking polymeric arrangement of the C domains in fibrin. These oligomers and those prepared with tissue transglutaminase were used to establish a mechanism of the C domain–mediated interaction of fibrin with endothelial cells. Cell adhesion and chemical cross-linking experiments revealed that oligomerization of the C domains by both transglutaminases significantly increases their RGD (arginyl–glycyl–aspartate)–dependent interaction with endothelial V3 and to a lesser extent with V5 and 51 integrins. The oligomerization promotes integrin clustering, thereby increasing cell adhesion, spreading, formation of prominent peripheral focal contacts, and integrin-mediated activation of focal adhesion kinase (FAK) and extracellular signal-regulated kinase (ERK) signaling pathways. The enhanced integrin clustering is likely caused by ordered juxtaposition of RGD-containing integrin-binding sites upon oligomerization of the C domains and increased affinity of these domains for integrins. Our findings provide new insights into the mechanism of the C domain–mediated interaction of endothelial cells with fibrin and imply its potential involvement in cell migration. They also suggest a new role for transglutaminases in regulation of integrin-mediated adhesion and signaling via covalent modification of integrin ligands. CiteULike    Connotea    Del.icio.us    Digg    Reddit    Technorati    What's this? This article has been cited by other articles: U. Sen, N. Tyagi, P. K. Patibandla, W. L. Dean, S. C. Tyagi, A. M. Roberts, and D. Lominadze Fibrinogen-induced endothelin-1 production from endothelial cells Am J Physiol Cell Physiol, April 1, 2009; 296(4): C840 - C847. [Abstract] [Full Text] [PDF] J. Y. Fok, S. Ekmekcioglu, and K. Mehta Implications of tissue transglutaminase expression in malignant melanoma. Mol. Cancer Ther., June 1, 2006; 5(6): 1493 - 1503. [Abstract] [Full Text] [PDF] P. Panizzi, R. Friedrich, P. Fuentes-Prior, K. Richter, P. E. Bock, and W. Bode Fibrinogen Substrate Recognition by Staphylocoagulase{middle dot}(Pro)thrombin Complexes J. Biol. Chem., January 13, 2006; 281(2): 1179 - 1187. [Abstract] [Full Text] [PDF] J. Cho, J. L. Degen, B. S. Coller, and D. F. Mosher Fibrin but Not Adsorbed Fibrinogen Supports Fibronectin Assembly by Spread Platelets: EFFECTS OF THE INTERACTION OF {alpha}IIb{beta}3 WITH THE C TERMINUS OF THE FIBRINOGEN {gamma}-CHAIN J. Biol. Chem., October 21, 2005; 280(42): 35490 - 35498. [Abstract] [Full Text] [PDF]

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