Molecular and Cellular Biochemistry

, Volume 335, Issue 1, pp 235–247

Urokinase receptor expression involves tyrosine phosphorylation of phosphoglycerate kinase

Authors

  • Praveenkumar Shetty
    • Texas Lung Injury Institute, Department of Specialty Care ServicesThe University of Texas Health Science Center at Tyler
  • Thirunavukkarasu Velusamy
    • Texas Lung Injury Institute, Department of Specialty Care ServicesThe University of Texas Health Science Center at Tyler
  • Yashodhar P. Bhandary
    • Texas Lung Injury Institute, Department of Specialty Care ServicesThe University of Texas Health Science Center at Tyler
  • Ming C. Liu
    • Department of Pharmacology, College of PharmacyThe University of Toledo
    • Texas Lung Injury Institute, Department of Specialty Care ServicesThe University of Texas Health Science Center at Tyler
Article

DOI: 10.1007/s11010-009-0273-4

Cite this article as:
Shetty, P., Velusamy, T., Bhandary, Y.P. et al. Mol Cell Biochem (2010) 335: 235. doi:10.1007/s11010-009-0273-4

Abstract

The interaction of urokinase-type plasminogen activator (uPA) with its receptor, uPAR, plays a central role in several pathophysiological processes, including cancer. uPA induces its own cell surface receptor expression through stabilization of uPAR mRNA. The mechanism involves binding of a 51 nt uPAR mRNA coding sequence with phosphoglycerate kinase (PGK) to down regulate cell surface uPAR expression. Tyrosine phosphorylation of PGK mediated by uPA treatment enhances uPAR mRNA stabilization. In contrast, inhibition of tyrosine phosphorylation augments PGK binding to uPAR mRNA and attenuates uPA-induced uPAR expression. Mapping the specific peptide region of PGK indicated that its first quarter (amino acids 1–100) interacts with uPAR mRNA. To determine if uPAR expression by uPA is regulated through activation of tyrosine residues of PGK, we mutated the specific tyrosine residue and tested mutant PGK for its ability to interfere with uPAR expression. Inhibition of tyrosine phosphorylation by mutating Y76 residue abolished uPAR expression induced by uPA treatment. These findings collectively demonstrate that Y76 residue present in the first quarter of the PGK molecule is involved in lung epithelial cell surface uPAR expression. This region can effectively mimic the function of a whole PGK molecule in inhibiting tumor cell growth.

Keywords

UrokinaseReceptormRNA stabilityPhosphoglycerate kinaseLung epithelial cell proliferation

Abbreviations

uPA

Urokinase-type plasminogen activator

uPAR

Urokinase-type plasminogen activator receptor

PGK

Phosphoglycerate kinase

hnRNPC

Heterogeneous nuclear ribonucleoprotein C

ECM

Extracellular matrix

PBS

Phosphate buffered saline

ECL

Enhanced chemiluminescence

SDS-PAGE

Sodium dodecylsulphate-polyacrylamide gel electrophoresis

IPTG

Isopropylthio-β-galactoside

TRI

Total RNA isolation

mRNA

Messenger RNA

DRB

5,6-Dichloro-1-β-D-ribofuranosyl benzimidazole

CDR

Coding region

ARE

AU rich element

UTR

Untranslated region

Copyright information

© Springer Science+Business Media, LLC. 2009