RDF/XMLNTriplesTurtleShow queryShare
SubjectPredicateObject
http://purl.uniprot.org/citations/22869372http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22869372http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/22869372http://www.w3.org/2000/01/rdf-schema#comment"Cystic fibrosis transmembrane conductance regulator (CFTR) Cl(-) channel mutations cause cystic fibrosis lung disease. A better understanding of CFTR regulatory mechanisms could suggest new therapeutic strategies. AMP-activated protein kinase (AMPK) binds to and phosphorylates CFTR, attenuating PKA-activated CFTR gating. However, the requirement for AMPK binding to CFTR and the potential role of other proteins in this regulation are unclear. We report that nucleoside diphosphate kinase A (NDPK-A) interacts with both AMPK and CFTR in overlay blots of airway epithelial cell lysates. Binding studies in Xenopus oocytes and transfected HEK-293 cells revealed that a CFTR peptide fragment that binds AMPK (CFTR-1420-57) disrupted the AMPK-CFTR interaction. Introduction of CFTR-1420-57 into human bronchial Calu-3 cells enhanced forskolin-stimulated whole cell conductance in patch clamp measurements. Similarly, injection of CFTR-1420-57 into Xenopus oocytes blocked the inhibition of cAMP-stimulated CFTR conductance by AMPK in two-electrode voltage clamp studies. AMPK also inhibited CFTR conductance with co-expression of WT NDPK-A in two-electrode voltage clamp studies, but co-expression of a catalytically inactive H118F mutant or various Ser-120 NDPK-A mutants prevented this inhibition. In vitro phosphorylation of WT NDPK-A was enhanced by purified active AMPK, but phosphorylation was prevented in H118F and phosphomimic Ser-120 NDPK-A mutants. AMPK does not appear to phosphorylate NDPK-A directly but rather promotes an NDPK-A autophosphorylation event that involves His-118 and Ser-120. Taken together, these results suggest that NDPK-A exists in a functional cellular complex with AMPK and CFTR in airway epithelia, and NDPK-A catalytic function is required for the AMPK-dependent regulation of CFTR."xsd:string
http://purl.uniprot.org/citations/22869372http://purl.org/dc/terms/identifier"doi:10.1074/jbc.m112.396036"xsd:string
http://purl.uniprot.org/citations/22869372http://purl.uniprot.org/core/author"Lee J."xsd:string
http://purl.uniprot.org/citations/22869372http://purl.uniprot.org/core/author"Lee J."xsd:string
http://purl.uniprot.org/citations/22869372http://purl.uniprot.org/core/author"Mehta A."xsd:string
http://purl.uniprot.org/citations/22869372http://purl.uniprot.org/core/author"Mehta A."xsd:string
http://purl.uniprot.org/citations/22869372http://purl.uniprot.org/core/author"Neumann D."xsd:string
http://purl.uniprot.org/citations/22869372http://purl.uniprot.org/core/author"Neumann D."xsd:string
http://purl.uniprot.org/citations/22869372http://purl.uniprot.org/core/author"Foskett J.K."xsd:string
http://purl.uniprot.org/citations/22869372http://purl.uniprot.org/core/author"Foskett J.K."xsd:string
http://purl.uniprot.org/citations/22869372http://purl.uniprot.org/core/author"Hallows K.R."xsd:string
http://purl.uniprot.org/citations/22869372http://purl.uniprot.org/core/author"Hallows K.R."xsd:string
http://purl.uniprot.org/citations/22869372http://purl.uniprot.org/core/author"Xiong S."xsd:string
http://purl.uniprot.org/citations/22869372http://purl.uniprot.org/core/author"Xiong S."xsd:string
http://purl.uniprot.org/citations/22869372http://purl.uniprot.org/core/author"Muimo R."xsd:string
http://purl.uniprot.org/citations/22869372http://purl.uniprot.org/core/author"Muimo R."xsd:string
http://purl.uniprot.org/citations/22869372http://purl.uniprot.org/core/author"King JD J.r."xsd:string
http://purl.uniprot.org/citations/22869372http://purl.uniprot.org/core/author"Riemen C.E."xsd:string
http://purl.uniprot.org/citations/22869372http://purl.uniprot.org/core/author"Riemen C.E."xsd:string
http://purl.uniprot.org/citations/22869372http://purl.uniprot.org/core/author"King J.D. Jr."xsd:string
http://purl.uniprot.org/citations/22869372http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22869372http://purl.uniprot.org/core/date"2012"xsd:gYear
http://purl.uniprot.org/citations/22869372http://purl.uniprot.org/core/name"J. Biol. Chem."xsd:string