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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...

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Autores principales: Mbom, Bertrade C., Siemers, Kathleen A., Ostrowski, Maggie A., Nelson, W. James, Barth, Angela I. M.
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
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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.
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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
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