Published ahead of print on June 19, 2003, doi:10.1165/rcmb.2002-0305OC
© 2004 American Thoracic Society DOI: 10.1165/rcmb.2002-0305OC Urokinase Receptor mRNA Stability Involves Tyrosine Phosphorylation in Lung Epithelial CellsDepartment of Specialty Care Services, The University of Texas Health Center at Tyler, Tyler, Texas Address correspondence to: Sreerama Shetty, Ph.D., Associate Professor of Medicine, University of Texas Health Center at Tyler, 11937 US HWY 271, Lab C-6, Tyler, TX, 75708. E-mail: sreerama.shetty{at}uthct.edu Interaction between urokinase-type plasminogen activator (uPA) and its receptor (uPAR) localizes cellular proteolysis and promotes cellular proliferation and migration, effects that may contribute to the pathogenesis of lung inflammation and neoplasia. Enhanced uPAR expression as well as stabilization of uPAR mRNA by transforming growth factor-ß and phorbol myristate acetate (PMA) shares a common mechanism involving phosphorylation and dephosphorylation of a uPAR mRNA-binding protein (uPAR mRNABp). PMA-induced tyrosine phosphorylation of the uPAR mRNABp inhibited the uPAR mRNA–uPAR mRNABp interaction, stabilized uPAR mRNA and enhanced uPAR protein expression. Downregulation of the uPAR mRNA and uPAR mRNABp interaction by PMA and transforming growth factor-ß can be reversed by pretreatment of cells with herbimycin which in turn inhibits expression of uPAR protein via a decrease in uPAR mRNA stability. Our experiments indicate that post-transcriptional regulation of uPAR expression requires activation of tyrosine kinases. Cytokines can regulate uPAR expression of lung-derived epithelial cells at the post-transcriptional level by tyrosine phosphorylation of the uPAR mRNA binding protein and may thereby influence tissue remodeling in lung injury or neoplasia.
Abbreviations: bronchial epithelial cells, Beas2B • bovine serum albumin, BSA • cycloheximide, cycD • glycosyl phospatidyl inositol, GPI • lipopolysaccharide, LPS • plasminogen activator inhibitor-1, PAI-1 • plasminogen activator inhibitor-2, PAI-2 • phosphate-buffered saline, PBS • phorbol myristate acetate, PMA • sodium dodecyl sulfate, SDS • SDS-polyacrylamide gel electrophoresis, SDS-PAGE • saline sodium citrate, SSC • transforming growth factor-ß, TGF-ß • tumor necrosis factor- This article has been cited by other articles:
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