title: Potential sites of CFTR activation by tyrosine kinases.
abstract: The CFTR chloride channel is tightly regulated by phosphorylation at multiple serine residues. Recently it has been proposed that its activity is also regulated by tyrosine kinases, however the tyrosine phosphorylation sites remain to be identified. In this study we examined 2 candidate tyrosine residues near the boundary between the first nucleotide binding domain and the R domain, a region which is important for channel function but devoid of PKA consensus sequences. Mutating tyrosines at positions 625 and 627 dramatically reduced responses to Src or Pyk2 without altering the activation by PKA, suggesting they may contribute to CFTR regulation.
authors.affiliation: a Department of Physiology , McGill University , Montreal , Quebec , Canada.|b CF Translational Research Center, McGill University , Montreal , Quebec , Canada.
authors.forename: Arnaud
authors.initials: A
authors.lastname: Billet
authors.affiliation: a Department of Physiology , McGill University , Montreal , Quebec , Canada.|b CF Translational Research Center, McGill University , Montreal , Quebec , Canada.
authors.forename: Yanlin
authors.initials: Y
authors.lastname: Jia
authors.affiliation: c Department of Biochemistry and Biophysics & CF Research Center , UNC Chapel Hill, Chapel Hill , NC , USA.
authors.forename: Timothy J
authors.initials: TJ
authors.lastname: Jensen
authors.affiliation: c Department of Biochemistry and Biophysics & CF Research Center , UNC Chapel Hill, Chapel Hill , NC , USA.
authors.forename: Yue-Xian
authors.initials: YX
authors.lastname: Hou
authors.affiliation: c Department of Biochemistry and Biophysics & CF Research Center , UNC Chapel Hill, Chapel Hill , NC , USA.
authors.forename: Xiu-Bao
authors.initials: XB
authors.lastname: Chang
authors.affiliation: c Department of Biochemistry and Biophysics & CF Research Center , UNC Chapel Hill, Chapel Hill , NC , USA.
authors.forename: John R
authors.initials: JR
authors.lastname: Riordan
authors.affiliation: a Department of Physiology , McGill University , Montreal , Quebec , Canada.|b CF Translational Research Center, McGill University , Montreal , Quebec , Canada.|d Research Institute of the McGill University Hospital Center , Montréal , Quebec , Canada.
authors.forename: John W
authors.initials: JW
authors.lastname: Hanrahan
mesh_terms: D000818:Animals; D002460:Cell Line; D006224:Cricetinae; D019005:Cystic Fibrosis Transmembrane Conductance Regulator / Q000235:genetics / Q000378:metabolism*; D055724:Electrophysiological Phenomena; D004789:Enzyme Activation; D016297:Mutagenesis, Site-Directed; D009154:Mutation; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*
chemical_list: D019005:Cystic Fibrosis Transmembrane Conductance Regulator; D011505:Protein-Tyrosine Kinases
keywords: CFTR regulation; Pyk2; Src; cystic fibrosis; phosphotyrosine