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This Article Full Text Full Text (PDF) All Versions of this Article: 292/2/L414    most recent 00121.2006v1 Alert me when this article is cited Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in ISI Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via ISI Web of Science (2) Citing Articles via Google Scholar Google Scholar Articles by Shetty, S. Articles by Shetty, P. K. Search for Related Content PubMed PubMed Citation Articles by Shetty, S. Articles by Shetty, P. K.

Regulation of urokinase receptor expression by protein tyrosine phosphatases

The Texas Lung Injury Institute, Department of Specialty Care Services, The University of Texas Health Center at Tyler, Tyler, Texas

Submitted 1 April 2006 ; accepted in final form 2 October 2006

Urokinase-type plasminogen activator (uPA) and its receptor (uPAR) play a major role in several physiological processes such as cell migration, proliferation, morphogenesis, and regulation of gene expression. Many of the biological activities of uPA depend on its association with uPAR. uPAR expression and its induction by uPA are regulated at the posttranscriptional level. Inhibition of protein tyrosine phosphatase-mediated dephosphorylation by sodium orthovanadate induces uPAR expression and, with uPA, additively induces cell surface uPAR expression. Sodium orthovanadate induces uPAR by increasing uPAR mRNA in a time- and concentration-dependent manner. Both sodium orthovanadate and uPA induce uPAR mRNA stability, indicating that dephosphorylation could contribute to uPA-induced posttranscriptional regulation of uPAR expression. Induction of the tyrosine phosphatase SHP2 in Beas2B and H157 cells inhibits basal cell surface uPAR expression and uPA-induced uPAR expression. Sodium orthovanadate also increases uPAR expression by decreasing the interaction of a uPAR mRNA coding region sequence with phosphoglycerate kinase (PGK) as well as by enhancing the interaction between a uPAR mRNA 3' untranslated sequence with heterogeneous nuclear ribonucleoprotein C (hnRNPC). On the contrary, overexpression of SHP2 in Beas2B cells increased interaction of PGK with the uPAR mRNA coding region and inhibited hnRNPC binding to the 3' untranslated sequence. These findings confirm a novel mechanism by which uPAR expression of lung airway epithelial cells is regulated at the level of mRNA stability by inhibition of protein tyrosine phosphatase-mediated dephosphorylation of uPAR mRNA binding proteins and demonstrate that the process involves SHP2.

phosphatase; messenger ribonucleic acid stability; messenger ribonucleic acid binding proteins

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