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http://purl.uniprot.org/citations/16716084http://www.w3.org/1999/02/22-rdf-syntax-ns#typehttp://purl.uniprot.org/core/Journal_Citation
http://purl.uniprot.org/citations/16716084http://www.w3.org/2000/01/rdf-schema#comment"Although recent studies show that the 14-3-3 protein is a negative regulator of ubiquitin E3 protein ligases, the molecular mechanism remains largely unknown. We previously demonstrated that 14-3-3 specifically binds one of the E3 enzymes, Nedd4-2 (a human gene product of KIAA0439, termed hNedd4-2), which can be phosphorylated by serum glucocorticoid-inducible protein kinase 1 (SGK1); this binding protects the phosphorylated/inactive hNedd4-2 from phosphatase-catalyzed dephosphorylation [Ichimura, T., et al. (2005) J. Biol. Chem. 280, 13187-13194]. Here we report an additional mechanism of 14-3-3-mediated regulation of hNedd4-2. Using surface plasmon resonance spectrometry, we show that 14-3-3 inhibits the interaction between the WW domains of hNedd4-2 and the PY motif of the epithelial Na(+) channel, ENaC. The inhibition was dose-dependent and was dependent on SGK1-catalyzed phosphorylation of Ser468 located between the WW domains. Importantly, a mutant of hNedd4-2, which can be phosphorylated by SGK1 but cannot bind 14-3-3, reduced SGK1-mediated stimulation of the ENaC-induced current in Xenopus laevis oocytes. In addition, 14-3-3 had similar effects on hNedd4-2 that had been phosphorylated by cAMP-dependent protein kinase (PKA). Our results, together with the recent finding on 14-3-3/parkin interactions [Sato, S., et al. (2006) EMBO J. 25, 211-221], suggest that 14-3-3 suppresses ubiquitin E3 ligase activities by inhibiting the formation of the enzyme/substrate complex."xsd:string
http://purl.uniprot.org/citations/16716084http://purl.org/dc/terms/identifier"doi:10.1021/bi052640q"xsd:string
http://purl.uniprot.org/citations/16716084http://purl.uniprot.org/core/author"Ichimura T."xsd:string
http://purl.uniprot.org/citations/16716084http://purl.uniprot.org/core/author"Isobe T."xsd:string
http://purl.uniprot.org/citations/16716084http://purl.uniprot.org/core/author"Saito T."xsd:string
http://purl.uniprot.org/citations/16716084http://purl.uniprot.org/core/author"Yamamura H."xsd:string
http://purl.uniprot.org/citations/16716084http://purl.uniprot.org/core/author"Hisanaga S."xsd:string
http://purl.uniprot.org/citations/16716084http://purl.uniprot.org/core/author"Taoka M."xsd:string
http://purl.uniprot.org/citations/16716084http://purl.uniprot.org/core/author"Shimada S."xsd:string
http://purl.uniprot.org/citations/16716084http://purl.uniprot.org/core/author"Nagaki K."xsd:string
http://purl.uniprot.org/citations/16716084http://purl.uniprot.org/core/date"2006"xsd:gYear
http://purl.uniprot.org/citations/16716084http://purl.uniprot.org/core/name"Biochemistry"xsd:string
http://purl.uniprot.org/citations/16716084http://purl.uniprot.org/core/pages"6733-6740"xsd:string
http://purl.uniprot.org/citations/16716084http://purl.uniprot.org/core/title"14-3-3 Mediates phosphorylation-dependent inhibition of the interaction between the ubiquitin E3 ligase Nedd4-2 and epithelial Na+ channels."xsd:string
http://purl.uniprot.org/citations/16716084http://purl.uniprot.org/core/volume"45"xsd:string
http://purl.uniprot.org/citations/16716084http://www.w3.org/2004/02/skos/core#exactMatchhttp://purl.uniprot.org/pubmed/16716084
http://purl.uniprot.org/citations/16716084http://xmlns.com/foaf/0.1/primaryTopicOfhttps://pubmed.ncbi.nlm.nih.gov/16716084
http://purl.uniprot.org/uniprot/#_A5X2V1-mappedCitation-16716084http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16716084
http://purl.uniprot.org/uniprot/#_B7Z6K0-mappedCitation-16716084http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16716084
http://purl.uniprot.org/uniprot/#_B7Z2P9-mappedCitation-16716084http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16716084
http://purl.uniprot.org/uniprot/#_P51170-mappedCitation-16716084http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16716084
http://purl.uniprot.org/uniprot/#_Q5XLQ3-mappedCitation-16716084http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16716084
http://purl.uniprot.org/uniprot/#_Q6LCK3-mappedCitation-16716084http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16716084
http://purl.uniprot.org/uniprot/#_Q6LCK4-mappedCitation-16716084http://www.w3.org/1999/02/22-rdf-syntax-ns#objecthttp://purl.uniprot.org/citations/16716084