Phosphorylation of Merlin by Aurora A kinase appears necessary for mitotic progression.
Aurora A
Merlin
Merlin/NF2
NF2
cancer biology
cell proliferation
ezrin
isoforms
mitosis
neurofibromatosis type 2
phosphorylation
tubulin
tumor suppressor gene
Journal
The Journal of biological chemistry
ISSN: 1083-351X
Titre abrégé: J Biol Chem
Pays: United States
ID NLM: 2985121R
Informations de publication
Date de publication:
30 08 2019
30 08 2019
Historique:
received:
30
11
2018
revised:
25
06
2019
pubmed:
13
7
2019
medline:
31
3
2020
entrez:
13
7
2019
Statut:
ppublish
Résumé
Although Merlin's function as a tumor suppressor and regulator of mitogenic signaling networks such as the Ras/rac, Akt, and Hippo pathways is well-documented, in mammals as well as in insects, its role during cell cycle progression remains unclear. In this study, using a combination of approaches, including FACS analysis, time-lapse imaging, immunofluorescence microscopy, and co-immunoprecipitation, we show that Ser-518 of Merlin is a substrate of the Aurora protein kinase A during mitosis and that its phosphorylation facilitates the phosphorylation of a newly discovered site, Thr-581. We found that the expression in HeLa cells of a Merlin variant that is phosphorylation-defective on both sites leads to a defect in centrosomes and mitotic spindles positioning during metaphase and delays the transition from metaphase to anaphase. We also show that the dual mitotic phosphorylation not only reduces Merlin binding to microtubules but also timely modulates ezrin interaction with the cytoskeleton. Finally, we identify several point mutants of Merlin associated with neurofibromatosis type 2 that display an aberrant phosphorylation profile along with defective α-tubulin-binding properties. Altogether, our findings of an Aurora A-mediated interaction of Merlin with α-tubulin and ezrin suggest a potential role for Merlin in cell cycle progression.
Identifiants
pubmed: 31296571
pii: S0021-9258(20)43235-1
doi: 10.1074/jbc.RA118.006937
pmc: PMC6721933
pii:
doi:
Substances chimiques
Benzazepines
0
MLN8054
0
Neurofibromin 2
0
AURKA protein, human
EC 2.7.11.1
Aurora Kinase A
EC 2.7.11.1
Nocodazole
SH1WY3R615
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
12992-13005Informations de copyright
© 2019 Mandati et al.
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