biostudies-literatureHara YMEXT | Japan Society for the Promotion of ScienceTMDU Young Innovative Medical Scientist UnitTakeda Science FoundationJapan Intractable Diseases (Nanbyo) Research FoundationJapan Agency for Medical Research and DevelopmentTMDU priority research areas grantPharmacodynamics Research FoundationUehara Memorial FoundationMSD Life Science Foundation, Public Interest Incorporated Foundatione2202125119https://www.ebi.ac.uk/biostudies/studies/S-EPMC9335246biostudies-literatureUnknown119(30)Protein kinase A (PKA) directly phosphorylates aquaporin-2 (AQP2) water channels in renal collecting ducts to reabsorb water from urine for the maintenance of systemic water homeostasis. More than 50 functionally distinct PKA-anchoring proteins (AKAPs) respectively create compartmentalized PKA signaling to determine the substrate specificity of PKA. Identification of an AKAP responsible for AQP2 phosphorylation is an essential step toward elucidating the molecular mechanisms of urinary concentration. PKA activation by several compounds is a novel screening strategy to uncover PKA substrates whose phosphorylation levels were nearly perfectly correlated with that of AQP2. The leading candidate in this assay proved to be an AKAP termed lipopolysaccharide-responsive and beige-like anchor proteProceedings of the National Academy of Sciences of the United States of AmericaLRBA is essential for urinary concentration and body water homeostasis.PMC93352462018A01JP19ek0109304JP19lm020302319H0104921H02933NoneKagechika HTokunaga FYanagawa HSuzuki SUchida SFujiki TYui NHara YSasaki SIchimura KOikawa DSakamaki YSohara ESusa KAndo FMori SMori TTakahashi MNanamatsu AMandai SRai TfalseLRBA is essential for urinary concentration and body water homeostasis.Protein kinase A (PKA) directly phosphorylates aquaporin-2 (AQP2) water channels in renal collecting ducts to reabsorb water from urine for the maintenance of systemic water homeostasis. More than 50 functionally distinct PKA-anchoring proteins (AKAPs) respectively create compartmentalized PKA signaling to determine the substrate specificity of PKA. Identification of an AKAP responsible for AQP2 phosphorylation is an essential step toward elucidating the molecular mechanisms of urinary concentration. PKA activation by several compounds is a novel screening strategy to uncover PKA substrates whose phosphorylation levels were nearly perfectly correlated with that of AQP2. The leading candidate in this assay proved to be an AKAP termed lipopolysaccharide-responsive and beige-like anchor prote2022-01-01T00:00:00Z2022 Jul2025-04-22T15:29:50.096Z2025-04-06T01:25:29.579ZS-EPMC93352463586245110.1073/pnas.2202125119