ArticleCellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology2009
Inhibition of protein kinase CK2 closes the CFTR Cl channel, but has no effect on the cystic fibrosis mutant deltaF508-CFTR.
Article in Cellular physiology and biochemistry : international journal of experimental cellular physiology, biochemistry, and pharmacology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 23 papers.
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Who cites it
23 citing papers in PubMed, 32 citations in OpenAlex.
- Regulation of CFTR stability at the plasma membrane-Mechanisms and therapeutic opportunities in cystic fibrosis.FEBS letters · 2026Review
- Protein kinase CK2: a potential therapeutic target for diverse human diseases.Signal transduction and targeted therapy · 2021Review
- Downfalls of Chemical Probes Acting at the Kinase ATP-Site: CK2 as a Case Study.Molecules (Basel, Switzerland) · 2021Review
- Protein kinase CK2 and ion channels (Review).Biomedical reports · 2020Review
- Article
- A posttranslational modification code for CFTR maturation is altered in cystic fibrosis.Science signaling · 2019Article
- NM23 proteins: innocent bystanders or local energy boosters for CFTR?Laboratory investigation; a journal of technical methods and pathology · 2018Review
- CK2 is a key regulator of SLC4A2-mediated ClPflugers Archiv : European journal of physiology · 2017Article
- In silico search for modifier genes associated with pancreatic and liver disease in Cystic Fibrosis.PloS one · 2017Article
- The New Role for an Old Kinase: Protein Kinase CK2 Regulates Metal Ion Transport.Pharmaceuticals (Basel, Switzerland) · 2016Review
- Trafficking and function of the cystic fibrosis transmembrane conductance regulator: a complex network of posttranslational modifications.American journal of physiology. Lung cellular and molecular physiology · 2016Review
- Investigating CFTR and KCa3.1 Protein/Protein Interactions.PloS one · 2016Article
- Regulatory Crosstalk by Protein Kinases on CFTR Trafficking and Activity.Frontiers in chemistry · 2016Review
- Paracellular transport through healthy and cystic fibrosis bronchial epithelial cell lines--do we have a proper model?PloS one · 2014Article
- CFTR mutations altering CFTR fragmentation.The Biochemical journal · 2013Article
- Role of binding and nucleoside diphosphate kinase A in the regulation of the cystic fibrosis transmembrane conductance regulator by AMP-activated protein kinase.The Journal of biological chemistry · 2012Article
- Structural models of CFTR-AMPK and CFTR-PKA interactions: R-domain flexibility is a key factor in CFTR regulation.Journal of molecular modeling · 2012Article
- Contribution of casein kinase 2 and spleen tyrosine kinase to CFTR trafficking and protein kinase A-induced activity.Molecular and cellular biology · 2011Article
- Understanding protein kinase CK2 mis-regulation upon F508del CFTR expression.Naunyn-Schmiedeberg's archives of pharmacology · 2011Review
- CFTR induces extracellular acid sensing in Xenopus oocytes which activates endogenous Ca²⁺-activated Cl⁻ conductance.Pflugers Archiv : European journal of physiology · 2011Article
Corrections and comments
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Authors and funding
11 authors at 7 institutions in 5 countries.
Funding
Abstract
backgroundDeletion of phenylalanine-508 (DeltaF508) from the first nucleotide-binding domain (NBD1) in the wild-type cystic fibrosis (CF) transmembrane-conductance regulator (wtCFTR) causes CF. However, the mechanistic relationship between DeltaF508-CFTR and the diversity of CF disease is unexplained. The surface location of F508 on NBD1 creates the potential for protein-protein interactions and nearby, lies a consensus sequence (SYDE) reported to control the pleiotropic protein kinase CK2.
methodsElectrophysiology, immunofluorescence and biochemistry applied to CFTR-expressing cells, Xenopus oocytes, pancreatic ducts and patient biopsies.
resultsIrrespective of PKA activation, CK2 inhibition (ducts, oocytes, cells) attenuates CFTR-dependent Cl(-) transport, closing wtCFTR in cell-attached membrane patches. CK2 and wtCFTR co-precipitate and CK2 co-localized with wtCFTR (but not DeltaF508-CFTR) in apical membranes of human airway biopsies. Comparing wild-type and DeltaF508CFTR expressing oocytes, only DeltaF508-CFTR Cl(-) currents were insensitive to two CK2 inhibitors. Furthermore, wtCFTR was inhibited by injecting a peptide mimicking the F508 region, whereas the DeltaF508-equivalent peptide had no effect.
conclusionsCK2 controls wtCFTR, but not DeltaF508-CFTR. Others find that peptides from the F508 region of NBD1 allosterically control CK2, acting through F508. Hence, disruption of CK2-CFTR interaction by DeltaF508-CFTR might disrupt multiple, membrane-associated, CK2-dependent pathways, creating a new molecular disease paradigm for deleted F508 in CFTR.
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