Published ahead of print on February 5, 2004, doi:10.1165/rcmb.2003-0104OC Am. J. Respir. Cell Mol. Biol., Volume 31, Number 1, July 2004, 100-106 A more recent version of this article appeared on July 1, 2004
Submitted on March 25, 2003 Regulation of Urokinase Receptor Expression by Phosphoglycerate KinaseSreerama Shetty1*,1 Specialty Care, University of Texas Health Center at Tyler, Tyler, TX, USA * To whom correspondence should be addressed. E-mail: sreerama.shetty{at}uthct.edu.
Posttranscriptional regulation represents a major mechanism by which eukaryotic gene expression is regulated through cis-trans interactions that serve as signals for rapid alterations of mRNA stability. Regulation of uPAR mRNA involves the interaction of a uPAR mRNA coding region sequence with a 50 kDa uPAR mRNA binding protein. We purified this protein from human bronchial epithelial (Beas2B) cells and identified it as phosphoglycerate kinase (PGK). We cloned PGK cDNA by polymerase chain reaction and expressed the recombinant PGK protein, which specifically bound the uPAR mRNA coding region by gel mobility shift and Northwestern blotting. We also confirmed a direct interaction of PGK protein with uPAR mRNA by immunoprecipitation. Overexpression of PGK in uPAR-overproducing H157 lung carcinoma cells resulted in decreased cytoplasmic uPAR mRNA and cell surface uPAR protein expression. Reduced uPAR mRNA expression involved decreased stability of the uPAR mRNA. Decline in 3H-thymidine incorporation and migration occurred in H157 cells transfected with PGK cDNA. These results demonstrate that PGK regulates uPAR expression at the posttranscriptional level.
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