Evidence map›Paper›PMID 21285348›Full record

ArticleThe Journal of biological chemistry2011

Sequential activation and inactivation of Dishevelled in the Wnt/beta-catenin pathway by casein kinases.

Ondrej Bernatik, Ranjani Sri Ganji, Jacomijn P Dijksterhuis, Peter Konik, Igor Cervenka, Tilman Polonio, Pavel Krejci, Gunnar Schulte, Vitezslav Bryja

Open access · hybridAbstract read
In one paragraph

Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 65 papers.

0numbers the graph read from it
0cells of the map it votes in
65citing papers in PubMed
4.9field-weighted citation impact, top 4% of its field
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

65 citing papers in PubMed, 112 citations in OpenAlex.

  1. Article
  2. Article
  3. Review
  4. Article
  5. Article
  6. Article
  7. Review
  8. The complex relationship of Wnt-signaling pathways and cilia.Current topics in developmental biology · 2023
    Article
  9. Review
  10. Article
  11. Article
  12. 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
  13. Article
  14. Article
  15. Article
  16. Review
  17. Article
  18. Primary Cilia Formation Does Not Rely on WNT/β-Catenin Signaling.Frontiers in cell and developmental biology · 2021
    Article
  19. Article
  20. Targeting Casein Kinase 1 (CK1) in Hematological Cancers.International journal of molecular sciences · 2020
    Review

5 more citing papers are in PubMed but not listed here.

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

9 authors at 4 institutions in 3 countries.

Ondrej BernatikInstitute of Experimental Biology, Masaryk University, 61137 Brno, Czech Republic.
Ranjani Sri Ganji
Jacomijn P Dijksterhuis
Peter Konik
Igor Cervenka
Tilman Polonio
Pavel Krejci
Gunnar Schulte
Vitezslav Bryja
Karolinska Institutet · SEMasaryk University · CZCzech Academy of Sciences, Institute of Biophysics · CZUniversity of South Bohemia in České Budějovice · CZ

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

Dishevelled (Dvl) is a key component in the Wnt/β-catenin signaling pathway. Dvl can multimerize to form dynamic protein aggregates, which are required for the activation of downstream signaling. Upon pathway activation by Wnts, Dvl becomes phosphorylated to yield phosphorylated and shifted (PS) Dvl. Both activation of Dvl in Wnt/β-catenin signaling and Wnt-induced PS-Dvl formation are dependent on casein kinase 1 (CK1) δ/ε activity. However, the overexpression of CK1 was shown to dissolve Dvl aggregates, and endogenous PS-Dvl forms irrespective of whether or not the activating Wnt triggers the Wnt/β-catenin pathway. Using a combination of gain-of-function, loss-of-function, and domain mapping approaches, we attempted to solve this discrepancy regarding the role of CK1ε in Dvl biology. We analyzed mutual interaction of CK1δ/ε and two other Dvl kinases, CK2 and PAR1, in the Wnt/β-catenin pathway. We show that CK2 acts as a constitutive kinase whose activity is required for the further action of CK1ε. Furthermore, we demonstrate that the two consequences of CK1ε phosphorylation are separated both spatially and functionally; first, CK1ε-mediated induction of TCF/LEF-driven transcription (associated with dynamic recruitment of Axin1) is mediated via a PDZ-proline-rich region of Dvl. Second, CK1ε-mediated formation of PS-Dvl is mediated by the Dvl3 C terminus. Furthermore, we demonstrate with several methods that PS-Dvl has decreased ability to polymerize with other Dvls and could, thus, act as the inactive signaling intermediate. We propose a multistep and multikinase model for Dvl activation in the Wnt/β-catenin pathway that uncovers a built-in de-activation mechanism that is triggered by activating phosphorylation of Dvl by CK1δ/ε.

Indexed as

Adaptor Proteins, Signal TransducingAnimalsbeta CateninCasein Kinase 1 epsilonCasein Kinase IdeltaCasein Kinase IIDishevelled ProteinsHEK293 CellsHumansMicePeptide MappingPhosphoproteinsPhosphorylationReceptor, PAR-1Signal TransductionWnt ProteinsAdaptor Proteins, Signal Transducingbeta CateninCasein Kinase 1 epsilonCasein Kinase IdeltaCasein Kinase IIDishevelled ProteinsDVL3 protein, humanDvl3 protein, mousePhosphoproteinsReceptor, PAR-1Wnt Proteins

Identifiers

PMID21285348
PMCPMC3060493
OpenAlexW1975481954

What OpenQuestion holds

Textmetadata
Read underepoch 390

Registered trials

None linked

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.