title: WNK4 phosphorylates ser(206) of claudin-7 and promotes paracellular Cl(-) permeability.
abstract: Mutations in WNK4 have been linked to hypertension in PHAII. Paracellular ion transport has been reported to be involved in this disease process; however, the specific molecular target has not been identified. In this study, we found that TJ protein claudin-7 and WNK4 were partially co-localized in renal tubules of rat kidney and co-immunoprecipitated in kidney epithelial cells. The wild-type and PHAII-causing mutant, but not the kinase-dead mutant, phosphorylated claudin-7. We have identified ser(206) in the COOH-terminus of claudin-7 as a putative phosphorylation site for WNK4. More importantly, disease-causing mutant enhanced claudin-7 phosphorylation and significantly increased paracellular permeability to Cl(-).
authors.affiliation: Department of Anatomy and Cell Biology, East Carolina University, Brody School of Medicine, Greenville, NC 27834, USA.
authors.forename: Rodney
authors.initials: R
authors.lastname: Tatum
authors.forename: Yuguo
authors.initials: Y
authors.lastname: Zhang
authors.forename: Qun
authors.initials: Q
authors.lastname: Lu
authors.forename: Kwonseop
authors.initials: K
authors.lastname: Kim
authors.forename: Beverly G
authors.initials: BG
authors.lastname: Jeansonne
authors.forename: Yan-Hua
authors.initials: YH
authors.lastname: Chen
mesh_terms: D000409:Alanine / Q000378:metabolism; D019943:Amino Acid Substitution; D000818:Animals; D002463:Cell Membrane Permeability / Q000502:physiology*; D002712:Chlorides / Q000378:metabolism*; D004848:Epithelium / Q000378:metabolism; D007668:Kidney / Q000166:cytology; D007684:Kidney Tubules / Q000378:metabolism; D018374:LLC-PK1 Cells; D008565:Membrane Proteins / Q000737:chemistry / Q000378:metabolism*; D016297:Mutagenesis, Site-Directed; D010766:Phosphorylation; D011233:Precipitin Tests; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D012694:Serine / Q000378:metabolism*; D013552:Swine; D019108:Tight Junctions / Q000502:physiology
chemical_list: D002712:Chlorides; D008565:Membrane Proteins; D012694:Serine; C499025:Wnk4 protein, rat; D017346:Protein Serine-Threonine Kinases; D000409:Alanine