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

ABSTRACT: We used human embryonic kidney HEK293T cells transfected with human GPR35 cDNAs as baits that were engineered to express Strep or hemagglutinin (HA) tags at the C terminus to perform an unbiased proteomics survey for GPR35 interaction partners.

INSTRUMENT(S): LTQ Orbitrap Velos

ORGANISM(S): Homo Sapiens (human)

TISSUE(S): Epithelial Cell

SUBMITTER: Georg Schneditz

LAB HEAD: Arthur Kaser

PROVIDER: PXD011269 | Pride | 2019-11-12

REPOSITORIES: Pride

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			Action	DRS
	P051_3916wa1sGM35_WT_L1_1.raw	Raw
	P051_3916wa3sGM35_108_L2_1.raw	Raw
	P051_3916wa5sEV_L3_1.raw	Raw
	P051_3916wa7sGM35_HA_L4_1.raw	Raw
	P051_3916wa7sGM35_HA_L4_2.raw	Raw

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

Schneditz Georg G Elias Joshua E JE Pagano Ester E Zaeem Cader M M Saveljeva Svetlana S Long Kathleen K Mukhopadhyay Subhankar S Arasteh Maryam M Lawley Trevor D TD Dougan Gordon G Bassett Andrew A Karlsen Tom H TH Kaser Arthur A Kaneider Nicole C NC

Science signaling 20190101 562

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 Ca<sup>2+</sup> to maximal levels and reduced Src activation and overall metabolic activity in macrophage ...[more]

PMID: 30600262

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Crystal structure of the sodium-potassium pump (Na+,K+-ATPase) with bound potassium and ouabain.

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

Project description: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, inflammatory diseases with a high cancer risk. GPR35 promoted homeostatic IEC turnover, whereas Gpr35 deletion or inhibition by a selective pepducin prevented inflammation-associated and spontaneous intestinal tumorigenesis in mice. Thus, GPR35 acts as a central signaling and metabolic pacesetter, which reveals an unexpected role of Na/K-ATPase in macrophage and IEC biology.

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