title: Casein kinase 2 specifically binds to and phosphorylates the carboxy termini of ENaC subunits.
abstract: A number of findings have suggested the involvement of protein phosphorylation in the regulation of the epithelial Na+ channel (ENaC). A recent study has demonstrated that the C tails of the beta and gamma subunits of ENaC are subject to phosphorylation by at least three protein kinases [Shi, H., Asher, C., Chigaev, A., Yung, Y., Reuveny, E., Seger, R. & Garty, H. (2002) J. Biol. Chem. 277, 13539-13547]. One of them was identified as ERK which phosphorylates betaT613 and gammaT623 and affects the channel interaction with Nedd4. The current study identifies a second protein kinase as casein kinase 2 (CK2), or CK-2-like kinase. It phosphorylates betaS631, a well-conserved serine on the beta subunit. Such phosphorylation is observed both in vitro using glutathione-S-transferase-ENaC fusion proteins and in vivo in ENaC-expressing Xenopus oocytes. The gamma subunit is weakly phosphorylated by this protein kinase on another residue (gammaT599), and the C tail of alpha is not significantly phosphorylated by this kinase. Thus, CK2 may be involved in the regulation of the epithelial Na+ channel.
authors.affiliation: Department of Biological Chemistry, and Department of Biological Regulation, The Weizmann Institute of Science, Rehovot, Israel.
authors.forename: Haikun
authors.initials: H
authors.lastname: Shi
authors.forename: Carol
authors.initials: C
authors.lastname: Asher
authors.forename: Yuval
authors.initials: Y
authors.lastname: Yung
authors.forename: Luba
authors.initials: L
authors.lastname: Kligman
authors.forename: Eitan
authors.initials: E
authors.lastname: Reuveny
authors.forename: Rony
authors.initials: R
authors.lastname: Seger
authors.forename: Haim
authors.initials: H
authors.lastname: Garty
mesh_terms: D000595:Amino Acid Sequence; D000818:Animals; D047390:Casein Kinase II; D053503:Epithelial Sodium Channels; D005982:Glutathione Transferase / Q000378:metabolism; D008969:Molecular Sequence Data; D009865:Oocytes; D010766:Phosphorylation; D011485:Protein Binding; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D016415:Sequence Alignment; D015222:Sodium Channels / Q000378:metabolism*; D014981:Xenopus
chemical_list: D053503:Epithelial Sodium Channels; D015222:Sodium Channels; D005982:Glutathione Transferase; D047390:Casein Kinase II; D017346:Protein Serine-Threonine Kinases