Commercially Available Preparations of Recombinant Wnt3a Contain Non-Wnt Related Activities Which May Activate TGF-β Signaling

Jon M Carthy; Ulla Engström; Carl-Henrik Heldin; Aristidis Moustakas

doi:10.1002/jcb.25378

Commercially Available Preparations of Recombinant Wnt3a Contain Non-Wnt Related Activities Which May Activate TGF-β Signaling

J Cell Biochem. 2016 Apr;117(4):938-45. doi: 10.1002/jcb.25378. Epub 2015 Sep 22.

Authors

Jon M Carthy¹, Ulla Engström¹, Carl-Henrik Heldin¹, Aristidis Moustakas^{1

2}

Affiliations

¹ Ludwig Institute for Cancer Research, Science for Life Laboratory, Uppsala University, Box 595 Biomedical Center, SE-751 24, Uppsala, Sweden.
² Department of Medical Biochemistry and Microbiology, Science for Life Laboratory, Uppsala University, Box 582 Biomedical Center, SE-751 23, Uppsala, Sweden.

PMID: 26369756
DOI: 10.1002/jcb.25378

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.

Keywords: BMP; FIBROBLAST; SMAD; TGF-β; Wnt; Wnt3a.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Antibodies, Neutralizing / pharmacology
Artifacts*
Biotechnology / methods
Biotechnology / standards*
Bone Morphogenetic Protein 7 / antagonists & inhibitors
Bone Morphogenetic Protein 7 / genetics
Bone Morphogenetic Protein 7 / metabolism
Gene Expression Regulation
Intracellular Signaling Peptides and Proteins
Mice
NIH 3T3 Cells
Proteins / genetics
Proteins / metabolism
Pyrazoles / pharmacology
Pyridines / pharmacology
Quality Control
Quinolines / pharmacology
Recombinant Proteins / genetics
Recombinant Proteins / metabolism
Recombinant Proteins / pharmacology
Signal Transduction
Smad Proteins / genetics
Smad Proteins / metabolism
Transforming Growth Factor beta1 / agonists*
Transforming Growth Factor beta1 / antagonists & inhibitors
Transforming Growth Factor beta1 / genetics
Transforming Growth Factor beta1 / metabolism
Wnt3A Protein / genetics
Wnt3A Protein / metabolism
Wnt3A Protein / pharmacology*
beta Catenin / genetics
beta Catenin / metabolism

Substances

2-phenyl-4-(3-pyridin-2-yl-1H-pyrazol-4-yl)pyridine
Antibodies, Neutralizing
Bone Morphogenetic Protein 7
CTNNB1 protein, mouse
DMH1 compound
Intracellular Signaling Peptides and Proteins
Proteins
Pyrazoles
Pyridines
Quinolines
Recombinant Proteins
Smad Proteins
Transforming Growth Factor beta1
WD repeat containing planar cell polarity effector
Wnt3A Protein
Wnt3a protein, mouse
beta Catenin
bmp7 protein, mouse