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| The urokinase receptor is a major vitronectin-binding protein on endothelial cells |
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| Author(s): Kanse SM, Kost C, Wilhelm OG, Andreasen PA, Preissner KT |
| Source: EXPERIMENTAL CELL RESEARCH Volume: 224 Issue: 2 Pages: 344-353 Published: MAY 1 1996 |
| Times Cited: 194 References: 51 |
| Abstract: We have previously demonstrated that vitronectin (VN), a morphoregulatory protein in the vessel wall, is internalized and translocated to the subendothelial matrix by an integrin-independent mechanism (J. Histochem. Cytochem. 41, 1823-1832, 1993). The cell surface component which mediates the initial contact of VN with endothelial cells is defined here. The specific binding of VN to endothelial cells demonstrated the following properties: a threefold increase after phorbol ester treatment; 85% inhibition by pretreatment of cells with phosphatidylinositol-phospholipase C to release glycolipid-anchored surface proteins; a 90% inhibition by urokinase (u-PA) receptor blocking antibody, u-PA increased VN binding to cells due to an eightfold increase in the affinity of VN for the u-PA receptor. Structure-function studies showed that the amino-terminal fragment of u-PA, devoid of any proteolytic activity, mediated this effect. Active plasminogen activator inhibitor-1 (PAI-1), but not inactivated PAI-1, inhibited VN binding to cells and displaced VN that was prebound to endothelial cell monolayers. Similarly, VN binding to purified (immobilized) u-PA receptor, but not to integrin, was enhanced by u-PA and inhibited by PAC-1. Hence, the binding of soluble VN to endothelial cell surfaces is mediated by the u-PA receptor, and the relative concentrations of u-PA and PAI-1 are able to regulate the strength of this interaction. Endothelial cell adhesion to immobilized VN was found to be integrin-mediated without any involvement of the VN-uPA-receptor system. Hence, the interaction of VN with the u-PA receptor may be involved in the regulation of cellular processes necessary for endothelial cell invasion and migration at VN-rich extracellular matrix sites. (C) 1996 Academic Press, Inc. |
| Document Type: Article |
| Language: English |
Addresses:
1. MPI, KERCKHOFF KLIN, HAEMOSTASIS RES UNIT, D-61231 BAD NAUHEIM, GERMANY
2. TECH UNIV MUNICH, FRAUENKLIN, W-8000 MUNICH, GERMANY
3. AARHUS UNIV, DEPT MOLEC BIOL, DK-8000 AARHUS, DENMARK |
| Publisher: ACADEMIC PRESS INC JNL-COMP SUBSCRIPTIONS, 525 B ST, STE 1900, SAN DIEGO, CA 92101-4495 |
| Subject Category: Oncology; Cell Biology |
| IDS Number: UJ210 |
| ISSN: 0014-4827 |
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| | | | | | | | | Record from Web of Science® | | | | | | | | | |