WNT Unrelated Activities in Commercially Available Preparations of Recombinant WNT3a

Autoři: Cajanek, L., Adlerz, L., Bryja, V., Arenas, E.
Rok: 2010


WNT signaling pathways play an important role in both development and disease. By analyzing the signaling capabilities of commercially available WNT3a preparations towards the PI3K/AKT/GSK3 signaling pathway, we discovered unexpected inconsistencies from lot to lot of recombinant WNT3a. We provide evidence that: (I) The ability to trigger AKT/GSK3 signaling varies dramatically between different lots of WNT3a, without any variation in their ability to activate the canonical WNT/beta-catenin signaling. (2) sFRP I, a WNT signaling inhibitor, is unable to interfere with the activation of AKT/GSK3 signaling induced by some of the WNT3a lots. (3) Pharmacological inhibition of AKT/GSK3 phosphorylation by PI3K inhibitors fails to affect the stabilization of B-catenin, the central effector of the canonical WNT/beta-catenin signaling pathway. In summary, while all tested lots of recombinant WNT3a activated WNT/beta-catenin pathway, our results suggest that individual lots of recombinant WNT3a activate the PI3K/AKT/GSK3 pathway in a WNT-independent manner, hampering thus the analysis of regulation of PI3K/AKT/GSK3 by WNT ligand. J. Cell. Biochem. 111: 1077-1079, 2010. (C) 2010 Wiley-Liss, Inc.