Document Detail

Urokinase-type plasminogen activator up-regulates its own expression by endothelial cells and monocytes via the u-PAR pathway.
MedLine Citation:
PMID:  11672584     Owner:  NLM     Status:  MEDLINE    
Signal transduction by urokinase-type plasminogen activator (u-PA) bound to its cell receptor has been well established. In the present study, we found, for the first time to our knowledge, that u-PA promotes its own synthesis by endothelial cells and monocytes. This phenomenon was characterized and shown to involve the u-PA receptor (u-PAR) pathway. The finding may be of general importance, since most cells that express u-PAR also produce u-PA. Human umbilical vein endothelial cells (HUVECs), U937 monocytes, and human peripheral blood monocytes (PFMCs) were incubated with diisopropylfluorophosphate (DFP)-pretreated u-PA, the amino-terminal fragment (ATF) of u-PA, or the kringle domain. A threefold up-regulation of u-PA secretion and synthesis by u-PA or ATF was found. The predominant effect was expressed in HUVECs, in which u-PA mRNA was also up-regulated. The u-PA kringle domain had no effect on u-PA synthesis, leading to the conclusion that the EGF domain was responsible. This was also consistent with the additional finding that the u-PAR, to which the EGF domain binds, was necessary for the up-regulation. The results indicate that u-PA up-regulates itself via its EGF domain and u-PAR. The possibilities that the results were related to displacement of receptor-bound u-PA or the blocking of u-PA incorporation into the cells were excluded. A modest up-regulation of u-PAR was also associated with this phenomenon.
C Li; J Zhang; Y Jiang; V Gurewich; Y Chen; J N Liu
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Publication Detail:
Type:  Journal Article    
Journal Detail:
Title:  Thrombosis research     Volume:  103     ISSN:  0049-3848     ISO Abbreviation:  Thromb. Res.     Publication Date:  2001 Aug 
Date Detail:
Created Date:  2001-10-23     Completed Date:  2002-03-18     Revised Date:  2009-11-19    
Medline Journal Info:
Nlm Unique ID:  0326377     Medline TA:  Thromb Res     Country:  United States    
Other Details:
Languages:  eng     Pagination:  221-32     Citation Subset:  IM    
Institute of Molecular Medicine, Nanjing University, Nanjing 10008, China.
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MeSH Terms
Cell Line
Dose-Response Relationship, Drug
Endothelium, Vascular / cytology,  enzymology*
Feedback, Physiological*
Mannose-Binding Lectins*
Membrane Glycoproteins / physiology*
Monocytes / enzymology*
Peptide Fragments / pharmacology
Protein Structure, Tertiary / physiology
RNA, Messenger / metabolism
Receptors, Cell Surface / physiology*
Umbilical Veins / cytology
Up-Regulation / drug effects
Urokinase-Type Plasminogen Activator / biosynthesis*,  genetics,  pharmacology
Reg. No./Substance:
0/MRC2 protein, human; 0/Mannose-Binding Lectins; 0/Membrane Glycoproteins; 0/Peptide Fragments; 0/RNA, Messenger; 0/Receptors, Cell Surface; EC Plasminogen Activator

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