ArticleThe Journal of biological chemistry2015
Cell Polarity Kinase MST4 Cooperates with cAMP-dependent Kinase to Orchestrate Histamine-stimulated Acid Secretion in Gastric Parietal Cells.
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 22 citations in OpenAlex.
- LIMK2 promotes centrosome clustering and cancer progression by activating MST4-mediated phosphorylation of NPM1.Oncogene · 2025Article
- Akt-elicited phosphorylation of Acapin steers cell migration.Journal of molecular cell biology · 2025Article
- Review
- Kupffer Cell-derived IL6 Promotes Hepatocellular Carcinoma Metastasis Via the JAK1-ACAP4 Pathway.International journal of biological sciences · 2025Article
- Ribosomal modification protein rimK-like family member A activates betaine-homocysteine S-methyltransferase 1 to ameliorate hepatic steatosis.Signal transduction and targeted therapy · 2024Article
- Alteration of gastric microbiota and transcriptome in a rat with gastric intestinal metaplasia induced by deoxycholic acid.Frontiers in microbiology · 2023Article
- Article
- Celastrol inhibits ezrin-mediated migration of hepatocellular carcinoma cells.Scientific reports · 2020Article
- Acetylation of ezrin regulates membrane-cytoskeleton interaction underlying CCL18-elicited cell migration.Journal of molecular cell biology · 2020Article
- A Metformin-Responsive Metabolic Pathway Controls Distinct Steps in Gastric Progenitor Fate Decisions and Maturation.Cell stem cell · 2020Article
- MST4 kinase suppresses gastric tumorigenesis by limiting YAP activation via a non-canonical pathway.The Journal of experimental medicine · 2020Article
- Gastric Parietal Cell Physiology and Helicobacter pylori-Induced Disease.Gastroenterology · 2019Review
- Dynamic acetylation of the kinetochore-associated protein HEC1 ensures accurate microtubule-kinetochore attachment.The Journal of biological chemistry · 2019Article
- MST4 Predicts Poor Prognosis And Promotes Metastasis By Facilitating Epithelial-Mesenchymal Transition In Gastric Cancer.Cancer management and research · 2019Article
- Regulation of Transporters and Channels by Membrane-Trafficking Complexes in Epithelial Cells.Cold Spring Harbor perspectives in biology · 2017Review
- MST4 kinase phosphorylates ACAP4 protein to orchestrate apical membrane remodeling during gastric acid secretion.The Journal of biological chemistry · 2017Article
- Phosphorylation of PP1 Regulator Sds22 by PLK1 Ensures Accurate Chromosome Segregation.The Journal of biological chemistry · 2016Article
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Authors and funding
15 authors at 4 institutions in 2 countries.
Funding
Abstract
The digestive function of the stomach depends on acidification of the gastric lumen. Acid secretion into the lumen is triggered by activation of the PKA cascade, which ultimately results in the insertion of gastric H,K-ATPases into the apical plasma membranes of parietal cells. A coupling protein is ezrin, whose phosphorylation at Ser-66 by PKA is required for parietal cell activation. However, little is known regarding the molecular mechanism(s) by which this signaling pathway operates in gastric acid secretion. Here we show that PKA cooperates with MST4 to orchestrate histamine-elicited acid secretion by phosphorylating ezrin at Ser-66 and Thr-567. Histamine stimulation activates PKA, which phosphorylates MST4 at Thr-178 and then promotes MST4 kinase activity. Interestingly, activated MST4 then phosphorylates ezrin prephosphorylated by PKA. Importantly, MST4 is important for acid secretion in parietal cells because either suppression of MST4 or overexpression of non-phosphorylatable MST4 prevents the apical membrane reorganization and proton pump translocation elicited by histamine stimulation. In addition, overexpressing MST4 phosphorylation-deficient ezrin results in an inhibition of gastric acid secretion. Taken together, these results define a novel molecular mechanism linking the PKA-MST4-ezrin signaling cascade to polarized epithelial secretion in gastric parietal 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.