title: Commercially Available Preparations of Recombinant Wnt3a Contain Non-Wnt Related Activities Which May Activate TGF-β Signaling.
abstract: The Wnt ligands are a family of secreted signaling proteins which play key roles in a number of cellular processes under physiological and pathological conditions. Wnts bind to their membrane receptors and initiate a signaling cascade which leads to the nuclear localization and transcriptional activity of β-catenin. The development of purified recombinant Wnt ligands has greatly aided in our understanding of Wnt signaling and its functions in development and disease. In the current study, we identified non-Wnt related signaling activities which were present in commercially available preparations of recombinant Wnt3a. Specifically, we found that treatment of cultured fibroblasts with recombinant Wnt3a induced immediate activation of TGF-β and BMP signaling and this activity appeared to be independent of the Wnt ligand itself. Therefore, while purified recombinant Wnt ligands continue to be a useful tool for studying this signaling pathway, one must exercise a degree of caution when analyzing the results of experiments that utilize purified recombinant Wnt ligands.
authors.affiliation: Ludwig Institute for Cancer Research, Science for Life Laboratory, Uppsala University, Box 595 Biomedical Center, SE-751 24, Uppsala, Sweden.
authors.forename: Jon M
authors.initials: JM
authors.lastname: Carthy
authors.affiliation: Ludwig Institute for Cancer Research, Science for Life Laboratory, Uppsala University, Box 595 Biomedical Center, SE-751 24, Uppsala, Sweden.
authors.forename: Ulla
authors.initials: U
authors.lastname: Engström
authors.affiliation: Ludwig Institute for Cancer Research, Science for Life Laboratory, Uppsala University, Box 595 Biomedical Center, SE-751 24, Uppsala, Sweden.
authors.forename: Carl-Henrik
authors.initials: CH
authors.lastname: Heldin
authors.affiliation: Ludwig Institute for Cancer Research, Science for Life Laboratory, Uppsala University, Box 595 Biomedical Center, SE-751 24, Uppsala, Sweden.|Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Box 582 Biomedical Center, SE-751 23, Uppsala, Sweden.
authors.forename: Aristidis
authors.initials: A
authors.lastname: Moustakas
mesh_terms: D000818:Animals; D057134:Antibodies, Neutralizing / Q000494:pharmacology; D016477:Artifacts; D001709:Biotechnology / Q000379:methods / Q000592:standards*; D055419:Bone Morphogenetic Protein 7 / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D005786:Gene Expression Regulation; D047908:Intracellular Signaling Peptides and Proteins; D051379:Mice; D041681:NIH 3T3 Cells; D011506:Proteins / Q000235:genetics / Q000378:metabolism; D011720:Pyrazoles / Q000494:pharmacology; D011725:Pyridines / Q000494:pharmacology; D011786:Quality Control; D011804:Quinolines / Q000494:pharmacology; D011994:Recombinant Proteins / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology; D015398:Signal Transduction; D051785:Smad Proteins / Q000235:genetics / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000819:agonists* / Q000037:antagonists & inhibitors / Q000235:genetics / Q000378:metabolism; D060509:Wnt3A Protein / Q000235:genetics / Q000378:metabolism / Q000494:pharmacology*; D051176:beta Catenin / Q000235:genetics / Q000378:metabolism; D000099274:Frizzled-Related Proteins
chemical_list: D057134:Antibodies, Neutralizing; D055419:Bone Morphogenetic Protein 7; D047908:Intracellular Signaling Peptides and Proteins; D011506:Proteins; D011720:Pyrazoles; D011725:Pyridines; D011804:Quinolines; D011994:Recombinant Proteins; D051785:Smad Proteins; D053773:Transforming Growth Factor beta1; D060509:Wnt3A Protein; D051176:beta Catenin; D000099274:Frizzled-Related Proteins; C502971:2-phenyl-4-(3-pyridin-2-yl-1H-pyrazol-4-yl)pyridine; C495267:CTNNB1 protein, mouse; C583032:DMH1 compound; C555511:Wnt3a protein, mouse; C525820:bmp7 protein, mouse
keywords: BMP; FIBROBLAST; SMAD; TGF-β; Wnt; Wnt3a