HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Full Text (PDF) 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 Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by François, P. P. Articles by Krause, K.-H. Search for Related Content PubMed PubMed Citation Articles by François, P. P. Articles by Krause, K.-H.

J Biol Chem, Vol. 274, Issue 53, 37611-37619, December 31, 1999

Vitronectin Interaction with Glycosaminoglycans
KINETICS, STRUCTURAL DETERMINANTS, AND ROLE IN BINDING TO ENDOTHELIAL CELLS^*

Patrice P. François^§, Klaus T. Preissner^¶, Mathias Herrmann, Rosaria P. Haugland^**, P. Vaudaux, Daniel P. Lew, and Karl-Heinz Krause

From the  Division of Infectious Diseases,  Biology of Aging Laboratory, University Hospital Geneva, CH-1211 Geneva 14, Switzerland, ^¶ Haemostasis Research Unit, Kerckhoff-Klinik, Max-Planck-Institut, D-61231 Bad Nauheim, Germany, ^** Molecular Probes, Inc., Eugene, Oregon 97402, and  Institute for Medical Microbiology, University of Münster, D-48129 Münster, Germany

Vitronectin (VN) is a high affinity heparin-binding protein. The physiological role of this binding has hitherto received little attention, and its molecular determinants are subject to controversy. In this study, we characterized vitronectin interaction with heparin, heparin analogues, bacterial extracts, and cell surface glycosaminoglycans. As assessed by (i) fluorescence assays, (ii) precipitation with heparin-Sepharose beads, or (iii) Western blotting with antibodies against VN_347-361 (the heparin-binding site), we demonstrate an exposure of the VN heparin-binding site in multimeric but not monomeric vitronectin. Through its heparin-binding site, vitronectin also bound other glycosaminoglycans and Staphylococcus aureus extracts. The kinetics of heparin binding to vitronectin were complex. After a fast association phase ( = 0.3 s), a slow conversion of an unstable to a stable heparin-vitronectin complex ( = 180 s) occurred. Heparin binding kinetics and transition to a stable complex were mimicked by VN_347-361, demonstrating that this area is the fully functional heparin-binding site of vitronectin. Multimeric vitronectin bound to endothelial cells. This binding was blocked by soluble heparin and was not observed when endothelial cells were pretreated with glycosaminoglycan-removing enzymes. Glycosaminoglycan-dependent interaction of endothelial cells with multimeric vitronectin might be a relevant mechanism for removal of multimeric vitronectin from plasma. Conversion of an unstable to a stable glycosaminoglycan-vitronectin complex is likely to be relevant for association with endothelial cells under flow conditions.

---

^* This work was supported in part by Swiss National Science Foundation Grants 3100-45891.95/1, 3100-055805.98/1, and 3200-045810.95/1, by CIBA-GEIGY Jubiläums-Siftung, and by Deutsche Forschungsgemeinschaft Grant Pr 327/1-3.The costs of publication of this article were defrayed in part by the payment of page charges. The article must therefore be hereby marked "advertisement" in accordance with 18 U.S.C. Section 1734 solely to indicate this fact.

^§ To whom correspondence should be addressed: Division of Infectious Diseases, University Hospital of Geneva, CH-1211 Geneva 14, Switzerland. Tel.: 41-22-3729827; Fax: 41-22-3729830; E-mail: patrice.francois@hcuge.ch.

---

Copyright © 1999 by The American Society for Biochemistry and Molecular Biology, Inc.

This article has been cited by other articles:

				G. N. M. Hajj, M. H. Lopes, A. F. Mercadante, S. S. Veiga, R. B. da Silveira, T. G. Santos, K. C. B. Ribeiro, M. A. Juliano, S. G. Jacchieri, S. M. Zanata, et al. Cellular prion protein interaction with vitronectin supports axonal growth and is compensated by integrins J. Cell Sci., June 1, 2007; 120(11): 1915 - 1926. [Abstract] [Full Text] [PDF]

				K. H. Minor, C. R. Schar, G. E. Blouse, J. D. Shore, D. A. Lawrence, P. Schuck, and C. B. Peterson A Mechanism for Assembly of Complexes of Vitronectin and Plasminogen Activator Inhibitor-1 from Sedimentation Velocity Analysis J. Biol. Chem., August 5, 2005; 280(31): 28711 - 28720. [Abstract] [Full Text] [PDF]

				J. A. Kricker, C. L. Towne, S. M. Firth, A. C. Herington, and Z. Upton Structural and Functional Evidence for the Interaction of Insulin-Like Growth Factors (IGFs) and IGF Binding Proteins with Vitronectin Endocrinology, July 1, 2003; 144(7): 2807 - 2815. [Abstract] [Full Text] [PDF]

				A. Noble, C. Towne, L. Chopin, D. Leavesley, and Z. Upton Insulin-Like Growth Factor-II Bound to Vitronectin Enhances MCF-7 Breast Cancer Cell Migration Endocrinology, June 1, 2003; 144(6): 2417 - 2424. [Abstract] [Full Text] [PDF]

				M. Hussain, K. Becker, C. von Eiff, J. Schrenzel, G. Peters, and M. Herrmann Identification and Characterization of a Novel 38.5-Kilodalton Cell Surface Protein of Staphylococcus aureus with Extended-Spectrum Binding Activity for Extracellular Matrix and Plasma Proteins J. Bacteriol., December 1, 2001; 183(23): 6778 - 6786. [Abstract] [Full Text] [PDF]

				B. Sinha, P. Francois, Y.-A. Que, M. Hussain, C. Heilmann, P. Moreillon, D. Lew, K.-H. Krause, G. Peters, and M. Herrmann Heterologously Expressed Staphylococcus aureus Fibronectin-Binding Proteins Are Sufficient for Invasion of Host Cells Infect. Immun., December 1, 2000; 68(12): 6871 - 6878. [Abstract] [Full Text] [PDF]