Evidence map›Paper›PMID 31870452›Full record

ArticleCell communication and signaling : CCS2019

Comparative phosphorylation map of Dishevelled 3 links phospho-signatures to biological outputs.

Kateřina Hanáková, Ondřej Bernatík, Marek Kravec, Miroslav Micka, Jitender Kumar, Jakub Harnoš, Petra Ovesná, Petra Paclíková, Matěj Rádsetoulal, David Potěšil and 4 more

Abstract readComparative Study
In one paragraph

Article in Cell communication and signaling : CCS, 2019. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 22 papers.

0numbers the graph read from it
0cells of the map it votes in
22citing papers in PubMed
–field-weighted citation impact
1 · What the graph read from it

What it found

Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.

The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

The trial behind it

Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.

Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.

3 · Its place in the literature

Who cites it

22 citing papers in PubMed.

  1. Article
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  7. Review
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  9. Article
  10. Role of the Ror family receptors in Wnt5a signaling.In vitro cellular & developmental biology. Animal · 2024
    Review
  11. Article
  12. Article
  13. Superresolution microscopy localizes endogenous Dvl2 to Wnt signaling-responsive biomolecular condensates.Proceedings of the National Academy of Sciences of the United States of America · 2022
    Article
  14. Article
  15. Review
  16. Article
  17. Article
  18. Regulation of Dishevelled DEP domain swapping by conserved phosphorylation sites.Proceedings of the National Academy of Sciences of the United States of America · 2021
    Article
  19. Article
  20. Primary Cilia Formation Does Not Rely on WNT/β-Catenin Signaling.Frontiers in cell and developmental biology · 2021
    Article
4 · The record

Corrections and comments

PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.

5 · Who and what money

Authors and funding

14 authors.

Kateřina HanákováCEITEC-Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic.
Ondřej BernatíkDepartment of Experimental Biology, Faculty of Science, Masaryk University, Kotlářská 2, 611 37, Brno, Czech Republic.
Marek KravecDepartment of Experimental Biology, Faculty of Science, Masaryk University, Kotlářská 2, 611 37, Brno, Czech Republic.
Miroslav MickaDepartment of Experimental Biology, Faculty of Science, Masaryk University, Kotlářská 2, 611 37, Brno, Czech Republic.
Jitender KumarCEITEC-Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic.
Jakub HarnošDepartment of Experimental Biology, Faculty of Science, Masaryk University, Kotlářská 2, 611 37, Brno, Czech Republic.
Petra OvesnáInstitute of Biostatistics and Analyses, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Petra PaclíkováDepartment of Experimental Biology, Faculty of Science, Masaryk University, Kotlářská 2, 611 37, Brno, Czech Republic.
Matěj RádsetoulalDepartment of Experimental Biology, Faculty of Science, Masaryk University, Kotlářská 2, 611 37, Brno, Czech Republic.
David PotěšilCEITEC-Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic.
Konstantinos TripsianesCEITEC-Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic.
Lukáš ČajánekDepartment of Histology and Embryology, Faculty of Medicine, Masaryk University, Brno, Czech Republic.
Zbyněk ZdráhalCEITEC-Central European Institute of Technology, Masaryk University, Kamenice 5, 625 00, Brno, Czech Republic. zdrahal@sci.muni.cz.
Vítězslav BryjaDepartment of Experimental Biology, Faculty of Science, Masaryk University, Kotlářská 2, 611 37, Brno, Czech Republic. bryja@sci.muni.cz.ORCID 0000-0002-9136-5085

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

backgroundDishevelled (DVL) is an essential component of the Wnt signaling cascades. Function of DVL is controlled by phosphorylation but the molecular details are missing. DVL3 contains 131 serines and threonines whose phosphorylation generates complex barcodes underlying diverse DVL3 functions. In order to dissect the role of DVL phosphorylation we analyzed the phosphorylation of human DVL3 induced by previously reported (CK1ε, NEK2, PLK1, CK2α, RIPK4, PKCδ) and newly identified (TTBK2, Aurora A) DVL kinases.

methodsShotgun proteomics including TiO

resultsWe used quantitative mass spectrometry and calculated site occupancies and quantified phosphorylation of > 80 residues. Functional validation demonstrated the importance of CK1ε-induced phosphorylation of S268 and S311 for Wnt-3a-induced β-catenin activation. S630-643 cluster phosphorylation by CK1, NEK2 or TTBK2 is essential for even subcellular distribution of DVL3 when induced by CK1 and TTBK2 but not by NEK2. Further investigation showed that NEK2 utilizes a different mechanism to promote even localization of DVL3. NEK2 triggered phosphorylation of PDZ domain at S263 and S280 prevents binding of DVL C-terminus to PDZ and promotes an open conformation of DVL3 that is more prone to even subcellular localization.

conclusionsWe identify unique phosphorylation barcodes associated with DVL function. Our data provide an example of functional synergy between phosphorylation in structured domains and unstructured IDRs that together dictate the biological outcome. Video Abtract.

Indexed as

Cells, CulturedDishevelled ProteinsHEK293 CellsHumansMass SpectrometryNIMA-Related KinasesPhosphorylationProtein ConformationSignal TransductionDishevelled ProteinsDVL3 protein, humanNEK2 protein, humanNIMA-Related KinasesCK1DishevelledDVL3KinaseMass spectrometryNEK2PhosphorylationTTBK2Wnt

Identifiers

PMID31870452
PMCPMC6927192

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Registered trials

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.