Dependence of human vascular cell surface proteolysis on expression of the urokinase receptor

1996 ◽  
Vol 3 (4) ◽  
Author(s):  
Hirofumi Sawa ◽  
CraigH. Lundgren ◽  
StevenL. Brown ◽  
Satoshi Fujii
Keyword(s):  
Cell Surface ◽  
Urokinase Receptor ◽  
Vascular Cell ◽  
Cell Surface Proteolysis

The Urokinase Receptor: Involvement in Cell Surface Proteolysis and Cancer Invasion

1992 ◽  
Vol 667 (1 Plasminogen A) ◽  
pp. 13-31 ◽  
Author(s):  
VINCENT ELLIS ◽  
CHARLES PYKE ◽  
JENS ERIKSEN ◽  
HELENE SOLBERG ◽  
KELD DANØ
Keyword(s):  
Cell Surface ◽  
Cancer Invasion ◽  
Urokinase Receptor ◽  
Cell Surface Proteolysis

The urokinase receptor: Focused cell surface proteolysis, cell adhesion and signaling

FEBS Letters ◽  
2009 ◽  
Vol 584 (9) ◽  
pp. 1923-1930 ◽  
Author(s):  
Francesco Blasi ◽  
Nicolai Sidenius
Keyword(s):  
Cell Adhesion ◽  
Cell Surface ◽  
Urokinase Receptor ◽  
Cell Surface Proteolysis

Mechanisms of Signaling through Urokinase Receptor and the Cellular Response

1999 ◽  
Vol 82 (08) ◽  
pp. 305-311 ◽  
Author(s):  
Yuri Koshelnick ◽  
Monika Ehart ◽  
Hannes Stockinger ◽  
Bernd Binder
Keyword(s):  
Cell Surface ◽  
Proteolytic Activity ◽  
Tumor Invasion ◽  
Cellular Response ◽  
Transmembrane Protein ◽  
Urokinase Receptor ◽  
Biological Processes ◽  
In Vivo Models ◽  
Proteolytic Activation ◽  
Core Proteins

IntroductionThe urokinase-urokinase receptor (u-PA-u-PAR) system seems to play a crucial role in a number of biological processes, including local fibrinolysis, tumor invasion, angiogenesis, neointima and atherosclerotic plaque formation, inflammation, and matrix remodeling during wound healing and development.1-6 Binding of urokinase to its specific receptor provides cells with a localized proteolytic potential. It stimulates conversion of cell surface-bound plasminogen into active plasmin, which, in turn, is required for proteolytic degradation of basement membrane components, including fibronectin, collagen, laminin, and proteoglycan core proteins.7 Moreover, plasmin activates other matrix-degrading enzymes, such as matrix metalloproteinases.8 Overexpression of u-PA/u-PAR correlates with tumor invasion and metastasis formation,9-13 while reduction of cell-surface bound u-PA and inhibition of u-PAR expression leads to a significant decrease of invasive and metastatic activity.14 Specific antagonists that suppress binding of u-PA to u-PAR have been shown to inhibit cell-surface plasminogen activation, tumor growth, and angiogenesis both in vitro and in vivo models.15,16 Independently of its proteolytic activity, u-PA is implicated in many biological processes that seem to require u-PAR-mediated intracellular signal transduction, such as proliferation, chemotactic movement and adhesion, migration, and differentiation.17 Data obtained in the late 1980s indicated that u-PA not only provides cells with local proteolytic activity, but might also be capable of transducing signals to the cell.18-22 At that time, however, the u-PAR has just been isolated, cloned, and identified as a glycosylphosphatidylinositol (GPI)-linked protein and not a transmembrane protein. Signaling via the u-PAR was, therefore, regarded as being unlikely, and the effects of u-PA on cell proliferation18-22 were thought to be mediated by proteolytic activation of latent growth factors. The assumption of direct signaling via u-PAR was, in fact, considered controversial, until about 10 years later when a physical association between u-PAR and signaling proteins was found.23 From this report on, several proteins associated with u-PAR have been identified. Now, u-PAR seems to be part of a large “signalosome” associated and interacting with several proteins on both the outside and inside of the cell.

scholarly journals Vitronectin Concentrates Proteolytic Activity on the Cell Surface and Extracellular Matrix by Trapping Soluble Urokinase Receptor-Urokinase Complexes

Blood ◽  
1998 ◽  
Vol 91 (7) ◽  
pp. 2305-2312 ◽  
Author(s):  
Triantafyllos Chavakis ◽  
Sandip M. Kanse ◽  
Barbara Yutzy ◽  
H. Roger Lijnen ◽  
Klaus T. Preissner
Keyword(s):  
Monoclonal Antibody ◽  
Extracellular Matrix ◽  
Cell Surface ◽  
Plasminogen Activator ◽  
Umbilical Vein ◽  
Urokinase Receptor ◽  
Enzyme Linked Immunosorbent Assay ◽  
Tissue Remodelling ◽  
Amino Terminal ◽  
Plasminogen Activator Activity

Abstract Urokinase-type-plasminogen activator (uPA) and its receptor are localized in the vessel wall where they are involved in cellular activation and remodelling processes. Besides the cell surface glycolipid (GPI)-anchored urokinase receptor (uPAR), which binds uPA with high affinity, recent evidence points to the existence of soluble uPAR (suPAR), as well. In the present study, the origin, binding mechanism, and cellular effects of suPAR were examined. Under basal conditions human vascular smooth muscle cells (HVSMC), human umbilical vein endothelial cells (HUVEC), and monocytic cells released 0.1 to 2 ng/mL suPAR, which was increased twofold to fivefold after phorbol ester (PMA) stimulation, as measured by a function-dependent enzyme-linked immunosorbent assay (ELISA). suPAR alone did not bind to HVSMC or HUVEC, but reduced cellular uPA binding by 50% to 70%. However, after removal of GPI-uPAR with phosphatidylinositol-specific phospholipase C, suPAR dose-dependently increased uPA binding by fourfold to fivefold. This increase in binding was completely inhibited by vitronectin (VN) and by a monoclonal antibody against VN, but not by other matrix proteins or antibodies. Thus, VN-mediated uPA binding to cells was regulated by the ratio of soluble to surface-associated uPAR. In a uPAR-deficient cell line (LM-TK−), suPAR increased uPA binding up to 10-fold, whereas the truncated receptor lacking the amino-terminal uPA-binding domain was ineffective. The formation of a ternary uPA/suPAR/VN-complex on the cell surface and the free extracellular matrix could be inhibited by a monoclonal antibody against VN, as well as by plasminogen activator inhibitor-1 (PAI-1). Moreover, VN-mediated binding of the uPA/suPAR-complex led to a fivefold increase in plasminogen activator activity. Through this novel pathway, VN concentrates the uPA/suPAR-complex to cell surfaces and extracellular matrix sites, leading to the accumulation of plasminogen activator activity required for cell migration and tissue remodelling processes.

scholarly journals Targeting of Cell Surface Proteolysis of Collagen XVII Impedes Squamous Cell Carcinoma Progression

2018 ◽  
Vol 26 (1) ◽  
pp. 17-30 ◽  
Author(s):  
Célimène Galiger ◽  
Stefanie Löffek ◽  
Marc P. Stemmler ◽  
Jasmin K. Kroeger ◽  
Venugopal R. Mittapalli ◽  
...  
Keyword(s):  
Squamous Cell Carcinoma ◽  
Cell Surface ◽  
Cell Carcinoma ◽  
Squamous Cell ◽  
Collagen Xvii ◽  
Cell Surface Proteolysis

scholarly journals Lupus autoantibodies interact directly with distinct glomerular and vascular cell surface antigens

1996 ◽  
Vol 49 (5) ◽  
pp. 1214-1221 ◽  
Author(s):  
Denise M. D'Andrea ◽  
Brigitte Coupaye-Gerard ◽  
Thomas R. Kleyman ◽  
Mary H. Foster ◽  
Michael P. Madaio
Keyword(s):  
Cell Surface ◽  
Surface Antigens ◽  
Cell Surface Antigens ◽  
Vascular Cell

scholarly journals ECM and Cell Surface Proteolysis: Regulating Cellular Ecology

Cell ◽  
1997 ◽  
Vol 91 (4) ◽  
pp. 439-442 ◽  
Author(s):  
Zena Werb
Keyword(s):  
Cell Surface ◽  
Cell Surface Proteolysis

scholarly journals Proteolytically active streptococcal pyrogenic exotoxin B cleaves monocytic cell urokinase receptor and releases an active fragment of the receptor from the cell surface.

1994 ◽  
Vol 269 (48) ◽  
pp. 30682-30687
Author(s):  
B B Wolf ◽  
C A Gibson ◽  
V Kapur ◽  
I M Hussaini ◽  
J M Musser ◽  
...  
Keyword(s):  
Cell Surface ◽  
Urokinase Receptor ◽  
Monocytic Cell ◽  
Streptococcal Pyrogenic Exotoxin B ◽  
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