Details

Autor(en) / Beteiligte

• Maher, Meghan T
• Mo, Rigen
• Flozak, Annette S
• Peled, Ofra N
• Gottardi, Cara J
• Xu, Wenqing

Titel

Beta-catenin phosphorylated at serine 45 is spatially uncoupled from beta-catenin phosphorylated in the GSK3 domain: implications for signaling

Ist Teil von

• PloS one, 2010-04, Vol.5 (4), p.e10184-e10184

Ort / Verlag

United States: Public Library of Science

Erscheinungsjahr

2010

Link zum Volltext

Quelle

MEDLINE

Beschreibungen/Notizen

• C. elegans and Drosophila generate distinct signaling and adhesive forms of beta-catenin at the level of gene expression. Whether vertebrates, which rely on a single beta-catenin gene, generate unique adhesive and signaling forms at the level of protein modification remains unresolved. We show that beta-catenin unphosphorylated at serine 37 (S37) and threonine 41 (T41), commonly referred to as transcriptionally Active beta-Catenin (ABC), is a minor nuclear-enriched monomeric form of beta-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. Beta-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. Beta-catenin phosphorylated at T41/S45 and unphosphorylated at S37 and T41 is predominantly nuclear, while beta-catenin phosphorylated at S33/37/T41 is mostly cytoplasmic, suggesting that beta-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.