Research article summary (published 13 Mar 2007):

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

Full 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.

Author information

Author/s: Kurayoshi, Manabu (M); Yamamoto, Hideki (H); Izumi, Shunsuke (S); Kikuchi, Akira (A);

Affiliation: Department of Biochemistry, Graduate School of Biomedical Sciences, Hiroshima University, Hiroshima 734-8551, Japan.

Journal and publication information

Publication Type: Journal Article; Research Support, Non-U.S. Gov't

Journal: The Biochemical journal (Biochem J), published in England. (Language: eng)

Reference: 2007-Mar; vol 402 (issue 3) : pp 515-23

Dates: Created 2007/02/22; Completed 2007/03/19; Revised 2009/10/27;

PMID: 17117926, status: MEDLINE (last retrieval date: 10/27/2009, IMS Date: )

Sourced from the National Library of Medicine. Abstract text and other information may be subject to copyright.

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MeSH headings (categories)

This article was linked to the MESH Headings shown below.

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; genetics; isolation & purification; metabolism Sequence Alignment Signal Transduction TCF Transcription Factors - metabolism Wnt Proteins - chemistry; genetics; isolation & purification; metabolism

Associated Chemicals: Fatty Acids, Monounsaturated (0) ; Proto-Oncogene Proteins (0) ; TCF Transcription Factors (0) ; Tcf7L2 transcription factor (0) ; Wnt Proteins (0) ; Wnt5a protein, mouse (0) ; palmitoleic acid (2091-29-4)

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