journal.pone.0156877.PDF (12.16 MB)
Download file

Phosphorylations of Serines 21/9 in Glycogen Synthase Kinase 3α/β Are Not Required for Cell Lineage Commitment or WNT Signaling in the Normal Mouse Intestine

Download (12.16 MB)
journal contribution
posted on 26.07.2016, 15:46 by Fiona Hey, Susan Giblett, Stephanie Forrest, Chelsea Herbert, Catrin Pritchard
The WNT signalling pathway controls many developmental processes and plays a key role in maintenance of intestine renewal and homeostasis. Glycogen Synthase Kinase 3 (GSK3) is an important component of the WNT pathway and is involved in regulating β-catenin stability and expression of WNT target genes. The mechanisms underpinning GSK3 regulation in this context are not completely understood, with some evidence suggesting this occurs through inhibitory N-terminal serine phosphorylation in a similar way to GSK3 inactivation in insulin signaling. To investigate this in a physiologically relevant context, we have analysed the intestinal phenotype of GSK3 knockin mice in which N-terminal serines 21/9 of GSK3α/β have been mutated to non-phosphorylatable alanine residues. We show that these knockin mutations have very little effect on overall intestinal integrity, cell lineage commitment, β-catenin localization or WNT target gene expression although a small increase in apoptosis at villi tips is observed. Our results provide in vivo evidence that GSK3 is regulated through mechanisms independent of N-terminal serine phosphorylation in order for β-catenin to be stabilised.

History

Citation

PLoS One, 2016, 11 (6), e0156877

Author affiliation

/Organisation/COLLEGE OF MEDICINE, BIOLOGICAL SCIENCES AND PSYCHOLOGY/School of Medicine/Department of Cancer Studies and Molecular Medicine

Version

VoR (Version of Record)

Published in

PLoS One

Publisher

Public Library of Science

issn

1932-6203

Acceptance date

22/05/2016

Copyright date

2016

Available date

26/07/2016

Publisher version

http://journals.plos.org/plosone/article?id=10.1371/journal.pone.0156877

Language

en

Usage metrics

Categories

Keywords

Licence

Exports