Document Detail

Thrombin increases expression of urokinase receptor by activation of the thrombin receptor.
MedLine Citation:
PMID:  7558719     Owner:  NLM     Status:  MEDLINE    
PURPOSE: To investigate the effect of thrombin on the urokinase plasminogen activator receptor (u-PAR) in retinal pigment epithelial (RPE) cells. METHODS: The authors analyzed u-PAR mRNA by Northern blot hybridization. Retinal pigment epithelial cell surface u-PAR was assayed by measuring the amount of functional urokinase plasminogen activator (u-PA) bound to cells at saturation. Retinal pigment epithelial cells were derived from fetal retinal tissue and established in primary cell culture. RESULTS: Thrombin increased u-PAR mRNA 4-fold in RPE cells examined by Northern blot hybridization, whereas the amount of thrombin receptor mRNA was unchanged. Thrombin stimulated u-PA binding to RPE cells 2.5- to 5-fold in a time- and dose-dependent manner. Hirudin, a thrombin antagonist, completely blocked the effects of thrombin on u-PAR expression in RPE cells. Phosphatidylinositol phospholipase C treatment of RPE cells resulted in the abolition of thrombin-induced u-PA binding. Recombinant soluble u-PAR competitively inhibited two-chain u-PA binding to the surface of thrombin-treated RPE cells. A thrombin receptor agonist peptide (SFLLRNPNDKYEPF) also induced a 2.5-fold increase in binding of u-PA to the surface of RPE cells. CONCLUSION: Thrombin increases u-PAR expression by RPE cells by a mechanism involving activation of the seven transmembrane thrombin receptor.
Z Yang; R L Cohen; G M Lui; D A Lawrence; M A Shuman
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Publication Detail:
Type:  Journal Article; Research Support, Non-U.S. Gov't    
Journal Detail:
Title:  Investigative ophthalmology & visual science     Volume:  36     ISSN:  0146-0404     ISO Abbreviation:  Invest. Ophthalmol. Vis. Sci.     Publication Date:  1995 Oct 
Date Detail:
Created Date:  1995-11-06     Completed Date:  1995-11-06     Revised Date:  2010-03-24    
Medline Journal Info:
Nlm Unique ID:  7703701     Medline TA:  Invest Ophthalmol Vis Sci     Country:  UNITED STATES    
Other Details:
Languages:  eng     Pagination:  2254-61     Citation Subset:  IM    
Cancer Research Institute, University of California at San Francisco 94143-0128, USA.
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MeSH Terms
Amino Acid Sequence
Blotting, Northern
Cells, Cultured
Dose-Response Relationship, Drug
Molecular Sequence Data
Peptide Fragments
Pigment Epithelium of Eye / cytology,  drug effects,  metabolism*
Plasminogen Activators / biosynthesis*
RNA, Messenger / metabolism
Receptors, Cell Surface / biosynthesis*
Receptors, Thrombin / chemistry,  metabolism*
Receptors, Urokinase Plasminogen Activator
Recombinant Proteins
Thrombin / pharmacology*
Type C Phospholipases / pharmacology
Urokinase-Type Plasminogen Activator / biosynthesis
Reg. No./Substance:
0/PLAUR protein, human; 0/Peptide Fragments; 0/RNA, Messenger; 0/Receptors, Cell Surface; 0/Receptors, Thrombin; 0/Receptors, Urokinase Plasminogen Activator; 0/Recombinant Proteins; EC 3.1.4.-/Type C Phospholipases; EC 3.4.21.-/Plasminogen Activators; EC; EC Plasminogen Activator

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