GPR35 promotes glycolysis, proliferation, and oncogenic signaling by engaging with the sodium potassium pump.

ABSTRACT: The sodium potassium pump (Na/K-ATPase) ensures the electrochemical gradient of a cell through an energy-dependent process that consumes about one-third of regenerated ATP. We report that the G protein-coupled receptor GPR35 interacted with the α chain of Na/K-ATPase and promotes its ion transport and Src signaling activity in a ligand-independent manner. Deletion of Gpr35 increased baseline Ca²⁺ to maximal levels and reduced Src activation and overall metabolic activity in macrophages and intestinal epithelial cells (IECs). In contrast, a common T108M polymorphism in GPR35 was hypermorphic and had the opposite effects to Gpr35 deletion on Src activation and metabolic activity. The T108M polymorphism is associated with ulcerative colitis and primary sclerosing cholangitis, infla

SUBMITTER: Schneditz G 

PROVIDER: S-EPMC6364804 | biostudies-literature | 2019 Jan

REPOSITORIES: biostudies-literature