PMID- 10608816
OWN - NLM
STAT- MEDLINE
DCOM- 20000208
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 274
IP  - 53
DP  - 1999 Dec 31
TI  - Vitronectin interaction with glycosaminoglycans. Kinetics, structural
      determinants, and role in binding to endothelial cells.
PG  - 37611-9
AB  - 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 (tau = 0.3
      s), a slow conversion of an unstable to a stable heparin-vitronectin complex (tau
      = 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.
FAU - Francois, P P
AU  - Francois PP
AD  - Division of Infectious Diseases, University Hospital Geneva, CH-1211 Geneva 14,
      Switzerland. francois@hcuge.ch
FAU - Preissner, K T
AU  - Preissner KT
FAU - Herrmann, M
AU  - Herrmann M
FAU - Haugland, R P
AU  - Haugland RP
FAU - Vaudaux, P
AU  - Vaudaux P
FAU - Lew, D P
AU  - Lew DP
FAU - Krause, K H
AU  - Krause KH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Vitronectin)
RN  - 9005-49-6 (Heparin)
SB  - IM
MH  - Cells, Cultured
MH  - Endothelium, Vascular/cytology/*metabolism
MH  - Heparin/*metabolism
MH  - Humans
MH  - Kinetics
MH  - Protein Binding
MH  - Protein Conformation
MH  - Spectrometry, Fluorescence
MH  - Vitronectin/chemistry/*metabolism
EDAT- 1999/12/23 00:00
MHDA- 1999/12/23 00:01
CRDT- 1999/12/23 00:00
PHST- 1999/12/23 00:00 [pubmed]
PHST- 1999/12/23 00:01 [medline]
PHST- 1999/12/23 00:00 [entrez]
AID - 10.1074/jbc.274.53.37611 [doi]
AID - S0021-9258(19)52936-2 [pii]
PST - ppublish
SO  - J Biol Chem. 1999 Dec 31;274(53):37611-9. doi: 10.1074/jbc.274.53.37611.