Cargando…
Nek2 phosphorylates and stabilizes β-catenin at mitotic centrosomes downstream of Plk1
β-Catenin is a multifunctional protein with critical roles in cell–cell adhesion, Wnt signaling, and the centrosome cycle. Whereas the regulation of β-catenin in cell–cell adhesion and Wnt signaling are well understood, how β-catenin is regulated at the centrosome is not. NIMA-related protein kinase...
Autores principales: | , , , , |
---|---|
Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
The American Society for Cell Biology
2014
|
Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967981/ https://www.ncbi.nlm.nih.gov/pubmed/24501426 http://dx.doi.org/10.1091/mbc.E13-06-0349 |
_version_ | 1782309089676623872 |
---|---|
author | Mbom, Bertrade C. Siemers, Kathleen A. Ostrowski, Maggie A. Nelson, W. James Barth, Angela I. M. |
author_facet | Mbom, Bertrade C. Siemers, Kathleen A. Ostrowski, Maggie A. Nelson, W. James Barth, Angela I. M. |
author_sort | Mbom, Bertrade C. |
collection | PubMed |
description | β-Catenin is a multifunctional protein with critical roles in cell–cell adhesion, Wnt signaling, and the centrosome cycle. Whereas the regulation of β-catenin in cell–cell adhesion and Wnt signaling are well understood, how β-catenin is regulated at the centrosome is not. NIMA-related protein kinase 2 (Nek2), which regulates centrosome disjunction/splitting, binds to and phosphorylates β-catenin. Using in vitro and cell-based assays, we show that Nek2 phosphorylates the same regulatory sites in the N-terminus of β-catenin as glycogen synthase kinase 3β (GSK3β), which are recognized by a specific phospho-S33/S37/T41 antibody, as well as additional sites. Nek2 binding to β-catenin appears to inhibit binding of the E3 ligase β-TrCP and prevents β-catenin ubiquitination and degradation. Thus β-catenin phosphorylated by Nek2 is stabilized and accumulates at centrosomes in mitosis. We further show that polo-like kinase 1 (Plk1) regulates Nek2 phosphorylation and stabilization of β-catenin. Taken together, these results identify a novel mechanism for regulating β-catenin stability that is independent of GSK3β and provide new insight into a pathway involving Plk1, Nek2, and β-catenin that regulates the centrosome cycle. |
format | Online Article Text |
id | pubmed-3967981 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2014 |
publisher | The American Society for Cell Biology |
record_format | MEDLINE/PubMed |
spelling | pubmed-39679812014-06-16 Nek2 phosphorylates and stabilizes β-catenin at mitotic centrosomes downstream of Plk1 Mbom, Bertrade C. Siemers, Kathleen A. Ostrowski, Maggie A. Nelson, W. James Barth, Angela I. M. Mol Biol Cell Articles β-Catenin is a multifunctional protein with critical roles in cell–cell adhesion, Wnt signaling, and the centrosome cycle. Whereas the regulation of β-catenin in cell–cell adhesion and Wnt signaling are well understood, how β-catenin is regulated at the centrosome is not. NIMA-related protein kinase 2 (Nek2), which regulates centrosome disjunction/splitting, binds to and phosphorylates β-catenin. Using in vitro and cell-based assays, we show that Nek2 phosphorylates the same regulatory sites in the N-terminus of β-catenin as glycogen synthase kinase 3β (GSK3β), which are recognized by a specific phospho-S33/S37/T41 antibody, as well as additional sites. Nek2 binding to β-catenin appears to inhibit binding of the E3 ligase β-TrCP and prevents β-catenin ubiquitination and degradation. Thus β-catenin phosphorylated by Nek2 is stabilized and accumulates at centrosomes in mitosis. We further show that polo-like kinase 1 (Plk1) regulates Nek2 phosphorylation and stabilization of β-catenin. Taken together, these results identify a novel mechanism for regulating β-catenin stability that is independent of GSK3β and provide new insight into a pathway involving Plk1, Nek2, and β-catenin that regulates the centrosome cycle. The American Society for Cell Biology 2014-04-01 /pmc/articles/PMC3967981/ /pubmed/24501426 http://dx.doi.org/10.1091/mbc.E13-06-0349 Text en © 2014 Mbom et al. This article is distributed by The American Society for Cell Biology under license from the author(s). Two months after publication it is available to the public under an Attribution–Noncommercial–Share Alike 3.0 Unported Creative Commons License (http://creativecommons.org/licenses/by-nc-sa/3.0). “ASCB®,” “The American Society for Cell Biology®,” and “Molecular Biology of the Cell®” are registered trademarks of The American Society of Cell Biology. |
spellingShingle | Articles Mbom, Bertrade C. Siemers, Kathleen A. Ostrowski, Maggie A. Nelson, W. James Barth, Angela I. M. Nek2 phosphorylates and stabilizes β-catenin at mitotic centrosomes downstream of Plk1 |
title | Nek2 phosphorylates and stabilizes β-catenin at mitotic centrosomes downstream of Plk1 |
title_full | Nek2 phosphorylates and stabilizes β-catenin at mitotic centrosomes downstream of Plk1 |
title_fullStr | Nek2 phosphorylates and stabilizes β-catenin at mitotic centrosomes downstream of Plk1 |
title_full_unstemmed | Nek2 phosphorylates and stabilizes β-catenin at mitotic centrosomes downstream of Plk1 |
title_short | Nek2 phosphorylates and stabilizes β-catenin at mitotic centrosomes downstream of Plk1 |
title_sort | nek2 phosphorylates and stabilizes β-catenin at mitotic centrosomes downstream of plk1 |
topic | Articles |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC3967981/ https://www.ncbi.nlm.nih.gov/pubmed/24501426 http://dx.doi.org/10.1091/mbc.E13-06-0349 |
work_keys_str_mv | AT mbombertradec nek2phosphorylatesandstabilizesbcateninatmitoticcentrosomesdownstreamofplk1 AT siemerskathleena nek2phosphorylatesandstabilizesbcateninatmitoticcentrosomesdownstreamofplk1 AT ostrowskimaggiea nek2phosphorylatesandstabilizesbcateninatmitoticcentrosomesdownstreamofplk1 AT nelsonwjames nek2phosphorylatesandstabilizesbcateninatmitoticcentrosomesdownstreamofplk1 AT barthangelaim nek2phosphorylatesandstabilizesbcateninatmitoticcentrosomesdownstreamofplk1 |