%0 Journal Article
%T ¦Â-Catenin Phosphorylated at Serine 45 Is Spatially Uncoupled from ¦Â-Catenin Phosphorylated in the GSK3 Domain: Implications for Signaling
%A Meghan T. Maher
%A Rigen Mo
%A Annette S. Flozak
%A Ofra N. Peled
%A Cara J. Gottardi
%J PLOS ONE
%D 2012
%I Public Library of Science (PLoS)
%R 10.1371/journal.pone.0010184
%X C. elegans and Drosophila generate distinct signaling and adhesive forms of ¦Â-catenin at the level of gene expression. Whether vertebrates, which rely on a single ¦Â-catenin gene, generate unique adhesive and signaling forms at the level of protein modification remains unresolved. We show that ¦Â-catenin unphosphorylated at serine 37 (S37) and threonine 41 (T41), commonly referred to as transcriptionally Active ¦Â-Catenin (ABC), is a minor nuclear-enriched monomeric form of ¦Â-catenin in SW480 cells, which express low levels of E-cadherin. Despite earlier indications, the superior signaling activity of ABC is not due to reduced cadherin binding, as ABC is readily incorporated into cadherin contacts in E-cadherin-restored cells. ¦Â-catenin phosphorylated at serine 45 (S45) or threonine 41 (T41) (T41/S45) or along the GSK3 regulatory cassette S33, S37 or T41 (S33/37/T41), however, is largely unable to associate with cadherins. ¦Â-catenin phosphorylated at T41/S45 and unphosphorylated at S37 and T41 is predominantly nuclear, while ¦Â-catenin phosphorylated at S33/37/T41 is mostly cytoplasmic, suggesting that ¦Â-catenin hypophosphorylated at S37 and T41 may be more active in transcription due to its enhanced nuclear accumulation. Evidence that phosphorylation at T41/S45 can be spatially separated from phosphorylations at S33/37/T41 suggests that these phosphorylations may not always be coupled, raising the possibility that phosphorylation at S45 serves a distinct nuclear function.
%U http://www.plosone.org/article/info%3Adoi%2F10.1371%2Fjournal.pone.0010184