Post-translational palmitoylation and glycosylation of Wnt-5a are necessary for its signalling

Biochem J. 2007 Mar 15;402(3):515-23. doi: 10.1042/BJ20061476.

Abstract

Wnt-5a is a representative ligand that activates a beta-catenin-independent pathway in Wnt signalling. In the present paper, the roles of the post-translational modifications in the actions of Wnt-5a were investigated. We found that Wnt-5a is modified with palmitate at Cys104 and glycans at Asn114, Asn120, Asn311 and Asn325. The palmitoylation was not essential for the secretion of Wnt-5a, but was necessary for its ability to suppress Wnt-3a-dependent T-cell factor transcriptional activity and to stimulate cell migration. Wnt-5a activated focal adhesion kinase and this activation also required palmitoylation. Wild-type Wnt-5a induced the internalization of Fz (Frizzled) 5, but a Wnt-5a mutant that lacks the palmitoylation site did not. Furthermore, the binding of Wnt-5a to the extracellular domain of Fz5 required palmitoylation of Wnt-5a. These results indicate that palmitoylation of Wnt-5a is important for the triggering of signalling at the cell surface level and, therefore, that the lipid-unmodified form of Wnt-5a cannot activate intracellular signal cascades. In contrast, glycosylation was necessary for the secretion of Wnt-5a, but not essential for the actions of Wnt-5a. Thus the post-translational palmitoylation and glycosylation of Wnt-5a are important for the actions and secretion of Wnt-5a.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Cell Line
  • Cell Movement
  • Fatty Acids, Monounsaturated / metabolism*
  • Glycosylation
  • Humans
  • Mice
  • Molecular Sequence Data
  • Protein Binding
  • Protein Processing, Post-Translational*
  • Proto-Oncogene Proteins / chemistry
  • Proto-Oncogene Proteins / genetics
  • Proto-Oncogene Proteins / isolation & purification
  • Proto-Oncogene Proteins / metabolism*
  • Sequence Alignment
  • Signal Transduction*
  • TCF Transcription Factors / metabolism
  • Transcription Factor 7-Like 2 Protein
  • Wnt Proteins / chemistry
  • Wnt Proteins / genetics
  • Wnt Proteins / isolation & purification
  • Wnt Proteins / metabolism*
  • Wnt-5a Protein

Substances

  • Fatty Acids, Monounsaturated
  • Proto-Oncogene Proteins
  • TCF Transcription Factors
  • TCF7L2 protein, human
  • Tcf7l2 protein, mouse
  • Transcription Factor 7-Like 2 Protein
  • Wnt Proteins
  • Wnt-5a Protein
  • Wnt5a protein, mouse
  • palmitoleic acid