Detailed Information on Publication Record
2016
Dishevelled is a NEK2 kinase substrate controlling dynamics of centrosomal linker proteins
ČERVENKA, Igor, Jana VALNOHOVÁ, Ondřej BERNATÍK, Jakub HARNOŠ, Matěj RÁDSETOULAL et. al.Basic information
Original name
Dishevelled is a NEK2 kinase substrate controlling dynamics of centrosomal linker proteins
Authors
ČERVENKA, Igor (703 Slovakia, belonging to the institution), Jana VALNOHOVÁ (203 Czech Republic, belonging to the institution), Ondřej BERNATÍK (203 Czech Republic, belonging to the institution), Jakub HARNOŠ (203 Czech Republic, belonging to the institution), Matěj RÁDSETOULAL (203 Czech Republic, belonging to the institution), Kateřina ŠEDOVÁ (203 Czech Republic, belonging to the institution), Kateřina HANÁKOVÁ (203 Czech Republic, belonging to the institution), David POTĚŠIL (203 Czech Republic, belonging to the institution), Miroslava SEDLÁČKOVÁ (203 Czech Republic, belonging to the institution), Alena SALAŠOVÁ (203 Czech Republic, belonging to the institution), Zachary STEINHART (124 Canada), Stephane ANGERS (124 Canada), Gunnar SCHULTE (276 Germany, belonging to the institution), Aleš HAMPL (203 Czech Republic, belonging to the institution), Zbyněk ZDRÁHAL (203 Czech Republic, belonging to the institution) and Vítězslav BRYJA (203 Czech Republic, guarantor, belonging to the institution)
Edition
Proceedings of the National Academy of Sciences of the United States of America, Washington, National Academy of Sciences, 2016, 0027-8424
Other information
Language
English
Type of outcome
Článek v odborném periodiku
Field of Study
10600 1.6 Biological sciences
Country of publisher
United States of America
Confidentiality degree
není předmětem státního či obchodního tajemství
Impact factor
Impact factor: 9.661
RIV identification code
RIV/00216224:14310/16:00088644
Organization unit
Faculty of Science
UT WoS
000381399200059
Keywords in English
Wnt signaling; centrosome; Dishevelled; NEK2; linker proteins
Tags
International impact, Reviewed
Změněno: 13/3/2018 15:33, Mgr. Lucie Jarošová, DiS.
Abstract
V originále
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.
Links
| EE2.3.20.0180, research and development project |
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| EE2.3.20.0185, research and development project |
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| GA13-32990S, research and development project |
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| GA15-21789S, research and development project |
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| GBP206/12/G151, research and development project |
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| LQ1601, research and development project |
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| MUNI/A/1398/2014, interní kód MU |
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| MUNI/M/1050/2013, interní kód MU |
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| 608180, interní kód MU |
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