ArticleThe Journal of biological chemistry2010
PKA regulates vacuolar H+-ATPase localization and activity via direct phosphorylation of the a subunit in kidney cells.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 61 papers.
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Who cites it
61 citing papers in PubMed, 102 citations in OpenAlex.
- F-actin-dependent activation of NADPH oxidase 5 by the vacuolar-type ATPase.The Journal of biological chemistry · 2026Article
- Therapeutic potential of cAMP-mediated lysosomal pH modulation in ATP6V1B2-related neuropathology.Cell death discovery · 2026Article
- Secretory stimuli distinctly regulate insulin secretory granule maturation through structural remodeling.Structure (London, England : 1993) · 2025Article
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- Pitolisant alleviates brain network dysfunction and cognitive deficits in a mouse model of Alzheimer's disease.Translational psychiatry · 2025Article
- The Emerging Roles of Vacuolar-Type ATPase-Dependent Lysosomal Acidification in Cardiovascular Disease.Biomolecules · 2025Review
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- Intercalated cell function, kidney innate immunity, and urinary tract infections.Pflugers Archiv : European journal of physiology · 2024Review
- Ionic regulatory strategies of crabs: the transition from water to land.Frontiers in physiology · 2024Review
- Impaired Autophagic Flux in Glucose-Deprived Cells: An Outcome of Lysosomal Acidification Failure Exacerbated by Mitophagy Dysfunction.Molecules and cells · 2023Review
- Plk1 promotes renal tubulointerstitial fibrosis by targeting autophagy/lysosome axis.Cell death & disease · 2023Article
- Defective lysosomal acidification: a new prognostic marker and therapeutic target for neurodegenerative diseases.Translational neurodegeneration · 2023Review
- Not all kidney cysts are created equal: a distinct renal cystogenic mechanism in tuberous sclerosis complex (TSC).Frontiers in physiology · 2023Review
- The V-ATPases in cancer and cell death.Cancer gene therapy · 2022Review
- Detection and quantification of the vacuolar H+ATPase using the Legionella effector protein SidK.The Journal of cell biology · 2022Article
- Cimetidine-induced androgenic failure causes cell death and changes in actin, EGF and V-ATPase immunoexpression in rat submandibular glands.Journal of anatomy · 2021Article
- The HAmerican journal of physiology. Cell physiology · 2021Review
- Regulation and function of V-ATPases in physiology and disease.Biochimica et biophysica acta. Biomembranes · 2020Review
- Adhesion-GPCR Gpr116 (ADGRF5) expression inhibits renal acid secretion.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- Review
1 more citing papers are in PubMed but not listed here.
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Authors and funding
12 authors at 3 institutions in 2 countries.
Funding
Abstract
The vacuolar H(+)-ATPase (V-ATPase) is a major contributor to luminal acidification in epithelia of Wolffian duct origin. In both kidney-intercalated cells and epididymal clear cells, cAMP induces V-ATPase apical membrane accumulation, which is linked to proton secretion. We have shown previously that the A subunit in the cytoplasmic V(1) sector of the V-ATPase is phosphorylated by protein kinase A (PKA). Here we have identified by mass spectrometry and mutagenesis that Ser-175 is the major PKA phosphorylation site in the A subunit. Overexpression in HEK-293T cells of either a wild-type (WT) or phosphomimic Ser-175 to Asp (S175D) A subunit mutant caused increased acidification of HCO(3)(-)-containing culture medium compared with cells expressing vector alone or a PKA phosphorylation-deficient Ser-175 to Ala (S175A) mutant. Moreover, localization of the S175A A subunit mutant expressed in HEK-293T cells was more diffusely cytosolic than that of WT or S175D A subunit. Acute V-ATPase-mediated, bafilomycin-sensitive H(+) secretion was up-regulated by a specific PKA activator in HEK-293T cells expressing WT A subunit in HCO(3)(-)-free buffer. In cells expressing the S175D mutant, V-ATPase activity at the membrane was constitutively up-regulated and unresponsive to PKA activators, whereas cells expressing the S175A mutant had decreased V-ATPase activity that was unresponsive to PKA activation. Finally, Ser-175 was necessary for PKA-stimulated apical accumulation of the V-ATPase in a polarized rabbit cell line of collecting duct A-type intercalated cell characteristics (Clone C). In summary, these results indicate a novel mechanism for the regulation of V-ATPase localization and activity in kidney cells via direct PKA-dependent phosphorylation of the A subunit at Ser-175.
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