Le, N.H., van der Bent, P., Huls, G., van de Wetering, M., Loghman-Adham, M., Ong, A.C.M., Calvet, J.P., Clevers, H., Breuning, M.H., van Dam, H. and Peters, D.J.M. (2004) Aberrant Polycystin-1 Expression Results in Modification of Activator Protein-1 Activity, whereas Wnt Signaling Remains Unaffected. Journal of Biological Chemistry, 279 (26). pp. 27472-27481. ISSN 1083-351X
Polycystin-1, the polycystic kidney disease 1 gene product, has been implicated in several signaling complexes that are known to regulate essential cellular functions. We investigated the role of polycystin-1 in Wnt signaling and activator protein-1 (AP-1) activation. To this aim, a membrane-targeted construct encoding the conserved C-terminal region of mouse polycystin- 1 reported to mediate signal transduction activity was expressed in human embryonic and renal epithelial cells. To ensure specificity and minimal cotransfection effects, we focused our study on the endogenous proteins that actually transduce the signals, -catenin and T-cell factor/lymphoid-enhancing factor for Wnt signaling and (phosphorylated) c-Jun, ATF2, and c-Fos for AP-1. Our data indicate that the C-terminal region of polycystin-1 activates AP-1 by inducing phosphorylation and expression of at least c-Jun and ATF2, whereas c-Fos was not affected. Under our experimental conditions, polycystin-1 did not modulate Wnt signaling. AP-1 activity was aberrant in human autosomal dominant polycystic kidney disease (ADPKD) renal cystic epithelial cells and in renal epithelial cells expressing transgenic full-length polycystin- 1, resulting in decreased Jun-ATF and increased Jun-Fos activity, whereas Wnt signaling remained unaffected. Since our data indicate that aberrant polycystin- 1 expression results in altered AP-1 activity, polycystin-1 may be required for adequate AP-1 activity.
|Copyright, Publisher and Additional Information:||Copyright © 2004 by the American Society for Biochemistry and Molecular Biology.|
|Institution:||The University of Sheffield|
|Academic Units:||The University of Sheffield > Faculty of Medicine, Dentistry and Health (Sheffield) > School of Medicine (Sheffield) > Clinical Sciences Division North (Sheffield) > Sheffield Kidney Institute|
|Depositing User:||Repository Officer|
|Date Deposited:||15 Aug 2005|
|Last Modified:||06 Jun 2014 19:51|