Murine Wnt-1 with an internal c-myc tag recombinantly produced in Escherichia coli can induce intracellular signaling of the canonical Wnt pathway in eukaryotic cells

J Biol Chem. 2004 Nov 12;279(46):47520-7. doi: 10.1074/jbc.M403207200. Epub 2004 Aug 26.

Abstract

Wnt-1 belongs to the Wnt family of secreted glycoproteins inducing an intracellular signaling pathway involved in cell proliferation, differentiation, and pattern formation. The canonical branch is one of three known branches. This is also valid in vitro, and Wnts can be considered beneficial for culturing primary cells from organs, provided Wnts are available and applicable even with cells of different species. It was shown here that internally c-myc-tagged murine Wnt-1 produced in the heterologous host Escherichia coli was appropriate for inducing intracellular signaling of the canonical Wnt pathway in eukaryotic cells via stabilization of cytosolic beta-catenin. The pioneering injection of the protein into the blastocoels of Xenopus laevis embryos led to axis duplication and suppression of head formation. Applying the recombinant murine Wnt-1 to metanephric mesenchyme activated the tubulogenic program. The signal-inducing activity of the recombinant protein was also positively demonstrated in the TOP-flash reporter assay. Although Wnts were purified recently from the growth media of stably transfected eukaryotic cell lines, the production of active Wnt proteins in pro- or eukaryotic microorganisms reportedly has never been successful. Here soluble production in E. coli and translocation into the oxidizing environment of the periplasm were achieved. The protein was purified using the internal c-myc tag. The effect on the eukaryotic cells implies that activity was retained. Thus, this approach could make recombinant murine Wnt-1 available as a good starting point for other Wnts needed, for example, for maintaining and differentiating stem cells, organ restoration therapy, and tissue engineering.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Embryo, Mammalian / anatomy & histology
  • Embryo, Mammalian / physiology
  • Embryo, Nonmammalian
  • Escherichia coli / genetics
  • Escherichia coli / metabolism*
  • Eukaryotic Cells / physiology*
  • Genes, Reporter
  • Humans
  • Intercellular Signaling Peptides and Proteins / genetics
  • Intercellular Signaling Peptides and Proteins / metabolism*
  • Mice
  • Morphogenesis / physiology
  • Proto-Oncogene Proteins c-myc / genetics
  • Proto-Oncogene Proteins c-myc / metabolism*
  • Recombinant Fusion Proteins / genetics
  • Recombinant Fusion Proteins / metabolism
  • Signal Transduction / physiology*
  • Wnt Proteins
  • Wnt1 Protein
  • Xenopus Proteins
  • Xenopus laevis / physiology

Substances

  • Intercellular Signaling Peptides and Proteins
  • Myc protein, mouse
  • Proto-Oncogene Proteins c-myc
  • Recombinant Fusion Proteins
  • WNT1 protein, Xenopus
  • WNT1 protein, human
  • Wnt Proteins
  • Wnt1 Protein
  • Wnt1 protein, mouse
  • Xenopus Proteins