ArticleProceedings of the National Academy of Sciences of the United States of America1998
Membrane targeting of cGMP-dependent protein kinase is required for cystic fibrosis transmembrane conductance regulator Cl- channel activation.
Article in Proceedings of the National Academy of Sciences of the United States of America, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 59 papers, 1 of them a synthesis that pooled it.
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Who cites it
59 citing papers in PubMed, 1 synthesis or guideline pooled it, 175 citations in OpenAlex.
- Efficacy and safety of Guanylyl cyclase C agonists (linaclotide and plecanatide) in patients with irritable bowel syndrome with constipation: a systematic review and meta-analysis of randomized controlled trials.Frontiers in pharmacology · 2026Pooled it
- A Randomized Phase III Clinical Trial of Plecanatide, a Uroguanylin Analog, in Patients With Chronic Idiopathic Constipation.The American journal of gastroenterology · 2017Trial
- Beyond the mutations: spatiotemporal regulation of CFTR by cAMP and calcium signaling in epithelial physiology and cystic fibrosis.Cellular & molecular biology letters · 2025Review
- Article
- Evaluation of F18 enterotoxigenicFrontiers in veterinary science · 2025Article
- Post-weaning diarrhea caused by F18Microbiome research reports · 2025Review
- Functional Consequences of CFTR Interactions in Cystic Fibrosis.International journal of molecular sciences · 2024Review
- Article
- Prkg2 regulates alveolar type 2-mediated re-alveolarization.Stem cell research & therapy · 2022Article
- Receptor Guanylyl Cyclase C and Cyclic GMP in Health and Disease: Perspectives and Therapeutic Opportunities.Frontiers in endocrinology · 2022Review
- Protein N-myristoylation: functions and mechanisms in control of innate immunity.Cellular & molecular immunology · 2021Review
- Guanylyl cyclase C as a biomarker for immunotherapies for the treatment of gastrointestinal malignancies.Biomarkers in medicine · 2021Review
- Porcine Enterotoxigenic Escherichia coli Strains Differ in Their Capacity To Secrete Enterotoxins through Varying YghG Levels.Applied and environmental microbiology · 2020Article
- Article
- Abnormal Uroguanylin Immunoreactive Cells Density in the Duodenum of Patients with Diarrhea-Predominant Irritable Bowel Syndrome Changes following Fecal Microbiota Transplantation.Gastroenterology research and practice · 2020Article
- Active PKG II inhibited the growth and migration of ovarian cancer cells through blocking Raf/MEK and PI3K/Akt signaling pathways.Bioscience reports · 2019Article
- Heat-Stable Enterotoxins of EnterotoxigenicToxins · 2019Review
- Selective inhibition of intestinal guanosine 3',5'-cyclic monophosphate signaling by small-molecule protein kinase inhibitors.The Journal of biological chemistry · 2018Article
- Transepithelial Fluid and Salt Re-Absorption Regulated by cGK2 Signals.International journal of molecular sciences · 2018Review
- Protein Kinases Type II (PKG II) Combined with L-Arginine Significantly Ameliorated Xenograft Tumor Development: Is L-Arginine a Potential Alternative in PKG II Activation?Medical science monitor : international medical journal of experimental and clinical research · 2018Article
Corrections and comments
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Authors and funding
10 authors at 2 institutions in 2 countries.
Funding
No grant is acknowledged in the PubMed record.
Abstract
A recently cloned isoform of cGMP-dependent protein kinase (cGK), designated type II, was implicated as the mediator of cGMP-provoked intestinal Cl- secretion based on its localization in the apical membrane of enterocytes and on its capacity to activate cystic fibrosis transmembrane conductance regulator (CFTR) Cl- channels. In contrast, the soluble type I cGK was unable to activate CFTR in intact cells, although both cGK I and cGK II could phosphorylate CFTR in vitro. To investigate the molecular basis for the cGK II isotype specificity of CFTR channel gating, we expressed cGK II or cGK I mutants possessing different membrane binding properties by using adenoviral vectors in a CFTR-transfected intestinal cell line, and we examined the ability of cGMP to phosphorylate and activate the Cl- channel. Mutation of the cGK II N-terminal myristoylation site (Gly2 --> Ala) reduced cGK II membrane binding and severely impaired cGK II activation of CFTR. Conversely, a chimeric protein, in which the N-terminal membrane-anchoring domain of cGK II was fused to the N terminus of cGK Ibeta, acquired the ability to associate with the membrane and activate the CFTR Cl- channel. The potency order of cGK constructs for activation of CFTR (cGK II > membrane-bound cGK I chimer >> nonmyristoylated cGK II > cGK Ibeta) correlated with the extent of 32P incorporation into CFTR observed in parallel measurements. These results strongly support the concept that membrane targeting of cGK is a major determinant of CFTR Cl- channel activation in intact cells.
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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.