Evidence map›Paper›PMID 21930781›Full record

ArticleMolecular and cellular biology2011

Contribution of casein kinase 2 and spleen tyrosine kinase to CFTR trafficking and protein kinase A-induced activity.

Simão Luz, Patthara Kongsuphol, Ana Isabel Mendes, Francisco Romeiras, Marisa Sousa, Rainer Schreiber, Paulo Matos, Peter Jordan, Anil Mehta, Margarida D Amaral and 2 more

Open access · bronzeAbstract read
In one paragraph

Article in Molecular and cellular biology, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.

0numbers the graph read from it
0cells of the map it votes in
26citing papers in PubMed
3.2field-weighted citation impact, top 8% 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

26 citing papers in PubMed, 38 citations in OpenAlex.

  1. Review
  2. Review
  3. Cell type-specific regulation of CFTR trafficking-on the verge of progress.Frontiers in cell and developmental biology · 2024
    Review
  4. Review
  5. A SYK/SHC1 pathway regulates the amount of CFTR in the plasma membrane.Cellular and molecular life sciences : CMLS · 2020
    Article
  6. Review
  7. Article
  8. Article
  9. Review
  10. Review
  11. Review
  12. CK2 is a key regulator of SLC4A2-mediated ClPflugers Archiv : European journal of physiology · 2017
    Article
  13. Article
  14. WNK signalling pathways in blood pressure regulation.Cellular and molecular life sciences : CMLS · 2017
    Review
  15. Review
  16. Review
  17. Review
  18. Regulation of the cystic fibrosis transmembrane conductance regulator anion channel by tyrosine phosphorylation.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015
    Article
  19. Article
  20. 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

12 authors at 4 institutions in 3 countries.

Simão LuzUniversity of Lisbon, BioFIG-Center for Biodiversity, Functional and Integrative Genomics, 1749-016 Lisbon, Portugal.
Patthara Kongsuphol
Ana Isabel Mendes
Francisco Romeiras
Marisa Sousa
Rainer Schreiber
Paulo Matos
Peter Jordan
Anil Mehta
Margarida D Amaral
Karl Kunzelmann
Carlos M Farinha
University of Lisbon · PTNational Institute of Health Dr. Ricardo Jorge · PTUniversity of Regensburg · DEUniversity of Dundee · GB

Funding

Wellcome Trust 069150/z/02/z
6 · The paper itself

Abstract

Previously, the pleiotropic "master kinase" casein kinase 2 (CK2) was shown to interact with CFTR, the protein responsible for cystic fibrosis (CF). Moreover, CK2 inhibition abolished CFTR conductance in cell-attached membrane patches, native epithelial ducts, and Xenopus oocytes. CFTR possesses two CK2 phosphorylation sites (S422 and T1471), with unclear impact on its processing and trafficking. Here, we investigated the effects of mutating these CK2 sites on CFTR abundance, maturation, and degradation coupled to effects on ion channel activity and surface expression. We report that CK2 inhibition significantly decreased processing of wild-type (wt) CFTR, with no effect on F508del CFTR. Eliminating phosphorylation at S422 and T1471 revealed antagonistic roles in CFTR trafficking: S422 activation versus T1471 inhibition, as evidenced by a severe trafficking defect for the T1471D mutant. Notably, mutation of Y512, a consensus sequence for the spleen tyrosine kinase (SYK) possibly acting in a CK2 context adjacent to the common CF-causing defect F508del, had a strong effect on both maturation and CFTR currents, allowing the identification of this kinase as a novel regulator of CFTR. These results reinforce the importance of CK2 and the S422 and T1471 residues for regulation of CFTR and uncover a novel regulation of CFTR by SYK, a recognized controller of inflammation.

Indexed as

AnimalsCasein Kinase IICricetinaeCyclic AMP-Dependent Protein KinasesCystic Fibrosis Transmembrane Conductance RegulatorIntracellular Signaling Peptides and ProteinsIon ChannelsMiceMice, Inbred C57BLMutationPhosphorylationProtein TransportProtein-Tyrosine KinasesSyk KinaseXenopus laevisCasein Kinase IICyclic AMP-Dependent Protein KinasesCystic Fibrosis Transmembrane Conductance RegulatorIntracellular Signaling Peptides and ProteinsIon ChannelsProtein-Tyrosine KinasesSyk KinaseSyk protein, mouse

Identifiers

PMID21930781
PMCPMC3209257
OpenAlexW2101026278

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.