Casein kinase 2 specifically binds to and phosphorylates the carboxy termini of ENaC subunits

• Published in: European journal of biochemistry Vol. 269; no. 18; pp. 4551 - 4558
• Main Authors: Shi, Haikun, Asher, Carol, Yung, Yuval, Kligman, Luba, Reuveny, Eitan, Seger, Rony, Garty, Haim
• Format: Journal Article
• Language: English
• Published: Oxford, UK Blackwell Science Ltd 01.09.2002
• Subjects: Amino Acid Sequence; Animals; casein; casein kinase 2; Casein Kinase II; ENaC; epithelial Na+ channel; Epithelial Sodium Channels; Glutathione Transferase - metabolism; mitogen-activated protein kinase; Molecular Sequence Data; Oocytes; Phosphorylation; Protein Binding; protein phosphorylation; Protein-Serine-Threonine Kinases - metabolism; Sequence Alignment; serine; sodium; Sodium Channels - metabolism; Xenopus
• ISSN: 0014-2956; 1432-1033
• DOI: 10.1046/j.1432-1033.2002.03154.x

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 β and γ 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 βT613 and γT623 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 βS631, a well‐conserved serine on the β subunit. Such phosphorylation is observed both in vitro using glutathione‐S‐transferase–ENaC fusion proteins and in vivo in ENaC‐expressing Xenopus oocytes. The γ subunit is weakly phosphorylated by this protein kinase on another residue (γT599), and the C tail of α is not significantly phosphorylated by this kinase. Thus, CK2 may be involved in the regulation of the epithelial Na+ channel.