Dishevelled is a NEK2 kinase substrate controlling dynamics of centrosomal linker proteins
The result's identifiers
Result code in IS VaVaI
<a href="https://www.isvavai.cz/riv?ss=detail&h=RIV%2F68081707%3A_____%2F16%3A00471960" target="_blank" >RIV/68081707:_____/16:00471960 - isvavai.cz</a>
Alternative codes found
RIV/00216224:14310/16:00088644
Result on the web
<a href="http://dx.doi.org/10.1073/pnas.1608783113" target="_blank" >http://dx.doi.org/10.1073/pnas.1608783113</a>
DOI - Digital Object Identifier
<a href="http://dx.doi.org/10.1073/pnas.1608783113" target="_blank" >10.1073/pnas.1608783113</a>
Alternative languages
Result language
angličtina
Original language name
Dishevelled is a NEK2 kinase substrate controlling dynamics of centrosomal linker proteins
Original language description
Dishevelled (DVL) is a key scaffolding protein and a branching point in Wnt signaling pathways. Here, we present conclusive evidence that DVL regulates the centrosomal cycle. We demonstrate that DVL dishevelled and axin (DIX) domain, but not DIX domain-mediated multimerization, is essential for DVL's centrosomal localization. DVL accumulates during the cell cycle and associates with NIMA-related kinase 2 (NEK2), which is able to phosphorylate DVL at amultitude of residues, as detected by a set of novel phospho-specific antibodies. This creates interfaces for efficient binding to CDK5 regulatory subunit-associated protein 2 (CDK5RAP2) and centrosomal Nek2-associated protein 1 (C-NAP1), two proteins of the centrosomal linker. Displacement of DVL from the centrosome and its release into the cytoplasm on NEK2 phosphorylation is coupled to the removal of linker proteins, an event necessary for centrosomal separation and proper formation of the mitotic spindle. Lack of DVL prevents NEK2-controlled dissolution of loose centrosomal linker and subsequent centrosomal separation. Increased DVL levels, in contrast, sequester centrosomal NEK2 and mimic monopolar spindle defects induced by a dominant negative version of this kinase. Our study thus uncovers molecular crosstalk between centrosome and Wnt signaling.
Czech name
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Czech description
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Classification
Type
J<sub>x</sub> - Unclassified - Peer-reviewed scientific article (Jimp, Jsc and Jost)
CEP classification
BO - Biophysics
OECD FORD branch
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Result continuities
Project
Result was created during the realization of more than one project. More information in the Projects tab.
Continuities
I - Institucionalni podpora na dlouhodoby koncepcni rozvoj vyzkumne organizace
Others
Publication year
2016
Confidentiality
S - Úplné a pravdivé údaje o projektu nepodléhají ochraně podle zvláštních právních předpisů
Data specific for result type
Name of the periodical
Proceedings of the National Academy of Sciences of the United States of America
ISSN
0027-8424
e-ISSN
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Volume of the periodical
113
Issue of the periodical within the volume
33
Country of publishing house
US - UNITED STATES
Number of pages
6
Pages from-to
9304-9309
UT code for WoS article
000381399200059
EID of the result in the Scopus database
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