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A urokinase‐sensitive region of the human urokinase receptor is responsible for its chemotactic activity
Author(s) -
Fazioli Francesca,
Resnati Massimo,
Sidenius Nicolai,
Higashimoto Yuichiro,
Appella Ettore,
Blasi Francesco
Publication year - 1997
Publication title -
the embo journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 7.484
H-Index - 392
eISSN - 1460-2075
pISSN - 0261-4189
DOI - 10.1093/emboj/16.24.7279
Subject(s) - biology , chemotaxis , urokinase , urokinase receptor , receptor , microbiology and biotechnology , biochemistry , genetics
The role of urokinase‐type plasminogen activator (uPA) and its receptor (uPAR/CD87) in cell migration and invasion is well substantiated. Recently, uPA has been shown to be essential in cell migration, since uPA −/− mice are greatly impaired in inflammatory cell recruitment. We have shown previously that the uPA‐induced chemotaxis requires interaction with and modification of uPAR/CD87, which is the true chemoattracting molecule acting through an unidentified cell surface component which mediates this cell surface chemokine activity. By expressing and testing several uPAR/CD87 variants, we have located and functionally characterized a potent uPAR/CD87 epitope that mimics the effects of the uPA–uPAR interaction. The chemotactic activity lies in the region linking domains 1 and 2, the only protease‐sensitive region of uPAR/CD87, efficiently cleaved by uPA at physiological concentrations. Synthetic peptides carrying this epitope promote chemotaxis and activate p56/p59 hck tyrosine kinase. Both chemotaxis and kinase activation are pertussis toxin sensitive, involving a G i/o protein in the pathway.