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This Article Full Text Full Text (PDF) All Versions of this Article: JOE-07-0262v1 197/3/543    most recent Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via Google Scholar Google Scholar Articles by Welters, H. J Articles by Morgan, N. G Search for Related Content PubMed PubMed Citation Articles by Welters, H. J Articles by Morgan, N. G

Institute of Biomedical and Clinical Science, Peninsula Medical School, Universities of Exeter and Plymouth, John Bull Building, Research Way, Plymouth PL6 8BU, UK¹ Department of Biochemistry II, Ruhr-University Bochum, 44780 Bochum, Germany² Institut fuer Zellbiologie (Tumorforschung), Universitaetsklinikum Essen, University of Duisburg-Essen, D-45122 Essen, Germany

(Correspondence should be addressed to H J Welters; Email: hannah.welters{at}pms.ac.uk)

In pancreatic β-cells, increased expression of the MODY5 gene product, HNF1β, leads to enhanced rates of apoptosis and altered regulation of the cell cycle, suggesting that control of HNF1β expression may be important for the control of β-cell proliferation and viability. It is unclear how these effects of HNF1β are mediated, but previously we have identified a protein tyrosine phosphatase, (PTP)-BL, as an HNF1β-regulated protein in β-cells and have now studied the role of this protein in INS-1 β-cells. Stably transfected cells were generated, which express either wild-type (WT) or a phosphatase-deficient mutant (PTP-BL-CS) of PTP-BL conditionally under the control of a tetracycline-regulated promoter. Enhanced expression of WT PTP-BL inhibited INS-1 cell growth dose dependently, but this effect was not observed when PTP-BL-CS was expressed. Neither construct altered the rate of apoptosis. PTP-BL has been reported to interact with components of the Wnt signalling pathway, and we observed that addition of exogenous Wnt3a resulted in an increase in cell proliferation and a rise in β-catenin levels, consistent with the operation of this pathway in INS-1 cells. Up-regulation of WT PTP-BL antagonised these responses but PTP-BL-CS failed to inhibit Wnt3a-induced proliferation. The rise in β-catenin caused by Wnt3a was also suppressed by over-expression of HNF1β, suggesting that HNF1β may interact with the Wnt signalling pathway via an increase in PTP-BL levels. We conclude that PTP-BL plays an important role in the regulation of cell cycle progression in pancreatic β-cells, and that it interacts functionally with components of the Wnt signalling pathway.