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...

Full description

Saved in:
Bibliographic Details
Published in:Molecular biology of the cell 2014-04, Vol.25 (7), p.977-991
Main Authors: Mbom, Bertrade C, Siemers, Kathleen A, Ostrowski, Maggie A, Nelson, W James, Barth, Angela I M
Format: Article
Language:English
Subjects:
beta Catenin - metabolism
Casein Kinase I - metabolism
Cell Cycle Proteins - metabolism
Centrosome - metabolism
Glycogen Synthase Kinase 3 - metabolism
Glycogen Synthase Kinase 3 beta
HCT116 Cells
HEK293 Cells
Humans
Mitosis
NIMA-Related Kinases
Phosphorylation
Polo-Like Kinase 1
Protein Serine-Threonine Kinases - metabolism
Protein Stability
Proto-Oncogene Proteins - metabolism
Sequence Deletion
Serine - metabolism
Spindle Apparatus - metabolism
Citations: Items that this one cites
Items that cite this one
Online Access:Get full text
Tags: Add Tag
No Tags, Be the first to tag this record!
Description
Summary: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.
ISSN:1059-1524
1939-4586
DOI:10.1091/mbc.E13-06-0349