title: WNT unrelated activities in commercially available preparations of recombinant WNT3a.
abstract: 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: (1) 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/β-catenin signaling. (2) sFRP1, 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 β-catenin, the central effector of the canonical WNT/β-catenin signaling pathway. In summary, while all tested lots of recombinant WNT3a activated WNT/β-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.
authors.affiliation: Karolinska Institute, Department of Medical Biochemistry and Biophysics, Molecular Neurobiology Unit, Stockholm, Sweden.
authors.forename: Lukas
authors.initials: L
authors.lastname: Cajanek
authors.forename: Linda
authors.initials: L
authors.lastname: Adlerz
authors.forename: Vitezslav
authors.initials: V
authors.lastname: Bryja
authors.forename: Ernest
authors.initials: E
authors.lastname: Arenas
mesh_terms: D004339:Drug Compounding; D038362:Glycogen Synthase Kinase 3; D006801:Humans; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D011994:Recombinant Proteins; D015398:Signal Transduction / Q000187:drug effects*; D051153:Wnt Proteins / Q000494:pharmacology*; D060508:Wnt3 Protein; D060509:Wnt3A Protein
chemical_list: D011994:Recombinant Proteins; C555510:WNT3A protein, human; D051153:Wnt Proteins; D060508:Wnt3 Protein; D060509:Wnt3A Protein; D019869:Phosphatidylinositol 3-Kinases; D051057:Proto-Oncogene Proteins c-akt; D038362:Glycogen Synthase Kinase 3