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Regulation of Urokinase Receptor Expression by Phosphoglycerate Kinase

Department of Specialty Care Services, University of Texas Health Center at Tyler, Tyler, Texas

Address correspondence to: Sreerama Shetty, Ph.D., Associate Professor of Medicine, The University of Texas Health Center at Tyler, 11937 US HWY 271, Lab C-6 Tyler, TX 75708. E-mail: sreerama.shetty{at}uthct.edu

Post-transcriptional regulation represents a major mechanism by which eukaryotic gene expression is regulated through cis-trans interactions that serve as signals for rapid alterations of messenger RNA (mRNA) stability. Regulation of urokinase-type plasminogen activator receptor (uPAR) mRNA involves the interaction of a uPAR mRNA coding region sequence with a 50 kD 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 post-transcriptional level.

Abbreviations: human bronchial epithelial cells, Beas2B • bovine serum albumin, BSA • fetal calf serum, FCS • isopropylthio-ß-galactoside, IPTG • messenger RNA, mRNA • plasmid complementary DNA, pcDNA • phosphoglycerate kinase, PGK • urokinase-type plasminogen activator, uPA • urokinase-type plasminogen activator receptor, uPAR • uPAR mRNA binding protein, uPAR mRNABp • untranslated region, UTR • sodium dodecysulfate, SDS • sodium dodecysulfate-polyacrylamide gel, SDS-PAGE • saline sidum citrate, SSC

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