Potential sites of CFTR activation by tyrosine kinases

Channels (Austin). 2016;10(3):247-51. doi: 10.1080/19336950.2015.1126010. Epub 2015 Dec 8.

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.

Keywords: CFTR regulation; Pyk2; Src; cystic fibrosis; phosphotyrosine.

Publication types

  • Research Support, N.I.H., Extramural
  • Research Support, Non-U.S. Gov't

MeSH terms

  • Animals
  • Cell Line
  • Cricetinae
  • Cystic Fibrosis Transmembrane Conductance Regulator / genetics
  • Cystic Fibrosis Transmembrane Conductance Regulator / metabolism*
  • Electrophysiological Phenomena
  • Enzyme Activation
  • Mutagenesis, Site-Directed
  • Mutation
  • Protein-Tyrosine Kinases / metabolism*

Substances

  • Cystic Fibrosis Transmembrane Conductance Regulator
  • Protein-Tyrosine Kinases