Nonreceptor tyrosine kinase ABL1 regulates lysosomal acidification by phosphorylating the ATP6V1B2 subunit of the vacuolar-type H⁺-ATPase.

ABSTRACT: The vacuolar-type H⁺-ATPase (V-ATPase) is a proton pump responsible for controlling the intracellular and extracellular pH of cells. Its activity and assembly are tightly controlled by multiple pathways, of which phosphorylation-mediated regulation is poorly understood. In this report, we show that in response to starvation stimuli, the nonreceptor tyrosine kinase ABL1 directly interacts with ATP6V1B2, a subunit of the V₁ domain of the V-ATPase, and phosphorylates ATP6V1B2 at Y68. Y68 phosphorylation in ATP6V1B2 facilitates the recruitment of the ATP6V1D subunit into the V₁ subcomplex of V-ATPase, therefore potentiating the assembly of the V₁ subcomplex with the membrane-embedded V₀ subcomplex to form the integrated functional V-ATPase

SUBMITTER: Song C 

PROVIDER: S-EPMC12087662 | biostudies-literature | 2025 Jun

REPOSITORIES: biostudies-literature