| ČERVENKA, Igor, Jana VALNOHOVÁ, Ondřej BERNATÍK, Jakub HARNOŠ, Matěj RÁDSETOULAL, Kateřina ŠEDOVÁ, Kateřina HANÁKOVÁ, David POTĚŠIL, Miroslava SEDLÁČKOVÁ, Alena SALAŠOVÁ, Zachary STEINHART, Stephane ANGERS, Gunnar SCHULTE, Aleš HAMPL, Zbyněk ZDRÁHAL and Vítězslav BRYJA. Dishevelled is a NEK2 kinase substrate controlling dynamics of centrosomal linker proteins. Proceedings of the National Academy of Sciences of the United States of America. Washington: National Academy of Sciences, 2016, vol. 113, No 33, p. 9304-9309. ISSN 0027-8424. Available from: https://dx.doi.org/10.1073/pnas.1608783113. |
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@article{1371626,
author = {Červenka, Igor and Valnohová, Jana and Bernatík, Ondřej and Harnoš, Jakub and Rádsetoulal, Matěj and Šedová, Kateřina and Hanáková, Kateřina and Potěšil, David and Sedláčková, Miroslava and Salašová, Alena and Steinhart, Zachary and Angers, Stephane and Schulte, Gunnar and Hampl, Aleš and Zdráhal, Zbyněk and Bryja, Vítězslav},
article_location = {Washington},
article_number = {33},
doi = {http://dx.doi.org/10.1073/pnas.1608783113},
keywords = {Wnt signaling; centrosome; Dishevelled; NEK2; linker proteins},
language = {eng},
issn = {0027-8424},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
title = {Dishevelled is a NEK2 kinase substrate controlling dynamics of centrosomal linker proteins},
volume = {113},
year = {2016}
}
TY - JOUR
ID - 1371626
AU - Červenka, Igor - Valnohová, Jana - Bernatík, Ondřej - Harnoš, Jakub - Rádsetoulal, Matěj - Šedová, Kateřina - Hanáková, Kateřina - Potěšil, David - Sedláčková, Miroslava - Salašová, Alena - Steinhart, Zachary - Angers, Stephane - Schulte, Gunnar - Hampl, Aleš - Zdráhal, Zbyněk - Bryja, Vítězslav
PY - 2016
TI - Dishevelled is a NEK2 kinase substrate controlling dynamics of centrosomal linker proteins
JF - Proceedings of the National Academy of Sciences of the United States of America
VL - 113
IS - 33
SP - 9304-9309
EP - 9304-9309
PB - National Academy of Sciences
SN - 00278424
KW - Wnt signaling
KW - centrosome
KW - Dishevelled
KW - NEK2
KW - linker proteins
N2 - 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.
ER -
ČERVENKA, Igor, Jana VALNOHOVÁ, Ondřej BERNATÍK, Jakub HARNOŠ, Matěj RÁDSETOULAL, Kateřina ŠEDOVÁ, Kateřina HANÁKOVÁ, David POTĚŠIL, Miroslava SEDLÁČKOVÁ, Alena SALAŠOVÁ, Zachary STEINHART, Stephane ANGERS, Gunnar SCHULTE, Aleš HAMPL, Zbyněk ZDRÁHAL and Vítězslav BRYJA. Dishevelled is a NEK2 kinase substrate controlling dynamics of centrosomal linker proteins. \textit{Proceedings of the National Academy of Sciences of the United States of America}. Washington: National Academy of Sciences, 2016, vol.~113, No~33, p.~9304-9309. ISSN~0027-8424. Available from: https://dx.doi.org/10.1073/pnas.1608783113.
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