Published ahead of print on June 19, 2003, doi:10.1165/rcmb.2002-0305OC
Am. J. Respir. Cell Mol. Biol., Volume 30, Number 1, January 2004, 69-75
A more recent version of this article appeared on January 1, 2004
Submitted on December 18, 2002
Revised on June 18, 2003
Urokinase Receptor mRNA Stability Involves Tyrosine Phosphorylation in Lung Epithelial Cells
Sreerama Shetty1* and Steven Idell1
1 Specialty Care Services, The University of Texas Health Center at Tyler, Tyler, Texas, USA
* To whom correspondence should be addressed. 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 TGF- and 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. Down regulation of the uPAR mRNA and uPAR mRNABp interaction by PMA and TGF- can be reversed by pre-treatment of cells with herbimycin which in turn inhibits expression of uPAR protein via a decrease in uPAR mRNA stability. Our experiments indicate that posttranscriptional regulation of uPAR expression requires activation of tyrosine kinases. Cytokines can regulate uPAR expression of lung-derived epithelial cells at the posttranscriptional level by tyrosine phosphorylation of the uPAR mRNA binding protein and may thereby influence tissue remodeling in lung injury or neoplasia.
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Copyright © 2003 American Thoracic Society.
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