Urokinase-type plasminogen activator up-regulates the expression of its cellular receptor through a post-transcriptional mechanism

We have recently reported that the urokinase-type plasminogen activator (uP A) up-regulates the cell surface expression of its own receptor (uPAR) in s everal cell types, independently of its enzymatic activity. uPA has no effe ct on kidney 293 cells which do not express uPAR and then cannot bind uPA. Kidney cells, transfected with the coding region of uPAR cDNA, express very large amounts of uPAR and respond to uPA stimulation by regulating uPAR bo th at mRNA and protein levels. uPA effect occurs also in the presence of th e transcriptional inhibitor dichloro-ribobenzimidazole, whereas it is aboli shed by the protein synthesis inhibitor cycloheximide. Moreover, uPA-depend ent uPAR up-regulation correlates with the increase of a complex between th e coding region of uPAR mRNA and an unknown cellular factor. We then propos e that uPA regulates uPAR expression at a post-transcriptional level, by pr omoting the binding of uPAR mRNA to a stabilizing factor. (C) 2001 Federati on of European Biochemical Societies. Published by Elsevier Science B.V. Al l rights reserved.