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 (uPA) up-regulates the cell surface expression of its own receptor (uPAR) in several cell types, independently of its enzymatic activity. uPA has no effect 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 both at mRNA and protein levels. uPA effect occurs also in the presence of the transcriptional inhibitor dichloro-ribobenzimidazole, whereas it is abolished by the protein synthesis inhibitor cycloheximide. Moreover, uPA-dependent uPAR up-regulation correlates with the increase of a complex between the coding region of uPAR mRNA and an unknown cellular factor. We then propose that uPA regulates uPAR expression at a post-transcriptional level, by promoting the binding of uPAR mRNA to a stabilizing factor.
Montuori
N
N
Centro di Endocrinologia ed Oncologia Sperimentale, Consiglio Nazionale delle Ricerche, Naples, Italy.
Mattiello
A
A
Mancini
A
A
Santoli
M
M
Taglialatela
P
P
Caputi
M
M
Rossi
G
G
Ragno
P
P
D020413:3' Untranslated Regions; D002460:Cell Line; D003513:Cycloheximide / Q000494:pharmacology; D006801:Humans; D007531:Isoflurophate / Q000494:pharmacology; D011401:Promoter Regions, Genetic; D011500:Protein Synthesis Inhibitors / Q000494:pharmacology; D012333:RNA, Messenger / Q000235:genetics / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000235:genetics* / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D020133:Reverse Transcriptase Polymerase Chain Reaction; D014158:Transcription, Genetic; D014162:Transfection; D015854:Up-Regulation; D014568:Urokinase-Type Plasminogen Activator / Q000378:metabolism / Q000494:pharmacology*
D020413:3' Untranslated Regions; C524898:PLAUR protein, human; D011500:Protein Synthesis Inhibitors; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D007531:Isoflurophate; D003513:Cycloheximide; D014568:Urokinase-Type Plasminogen Activator