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  • The EMBO Journal (1997) 16, 7279 - 7286
  • doi:10.1093/emboj/16.24.7279

A urokinase-sensitive region of the human urokinase receptor is responsible for its chemotactic activity

Francesca Fazioli1,2, Massimo Resnati1,2, Nicolai Sidenius1,2, Yuichiro Higashimoto3, Ettore Appella3 and Francesco Blasi1,2

  1. Department of Biology and Biotechnology (DIBIT), San Raffaele Scientific Institute, Via Olgettina 60, 20132 Milan, Italy
  2. Department of Genetics and Microbial Biology, University of Milan, Via Celoria 26, 20133 Milan, Italy
  3. Laboratory of Cell Biology, NCI, National Institutes of Health, Bethesda, MD 20892, USA

Correspondence to:

Francesco Blasi, E-mail: blasif@dibit.hsr.it

Received 9 August 1997; Revised 24 September 1997

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/p59hck tyrosine kinase. Both chemotaxis and kinase activation are pertussis toxin sensitive, involving a Gi/o protein in the pathway.

  • Keywords:

    • chemotaxis,
    • G protein,
    • pertussis toxin,
    • receptor,
    • urokinase-type plasminogen activator