title: Protein kinase CK2 interacts at the neuromuscular synapse with Rapsyn, Rac1, 14-3-3γ, and Dok-7 proteins and phosphorylates the latter two.
abstract: Previously, we demonstrated that the protein kinase CK2 associates with and phosphorylates the receptor tyrosine kinase MuSK (muscle specific receptor tyrosine kinase) at the neuromuscular junction (NMJ), thereby preventing fragmentation of the NMJs (Cheusova, T., Khan, M. A., Schubert, S. W., Gavin, A. C., Buchou, T., Jacob, G., Sticht, H., Allende, J., Boldyreff, B., Brenner, H. R., and Hashemolhosseini, S. (2006) Genes Dev. 20, 1800-1816). Here, we asked whether CK2 interacts with other proteins involved in processes at the NMJ, which would be consistent with the previous observation that CK2 appears enriched at the NMJ. We identified the following proteins to interact with protein kinase CK2: (a) the α and β subunits of the nicotinic acetylcholine receptors with weak interaction, (b) dishevelled (Dsh), and (c) another four proteins, Rapsyn, Rac1, 14-3-3γ, and Dok-7, with strong interaction. CK2 phosphorylated 14-3-3γ at serine residue 235 and Dok-7 at several serine residues but does not phosphorylate Rapsyn or Rac1. Furthermore, phosphomimetic Dok-7 mutants aggregated nicotinic acetylcholine receptors in C2C12 myotubes with significantly higher frequency than wild type Dok-7. Additionally, we mapped the interacting epitopes of all four binding partners to CK2 and thereby gained insights into the potential role of the CK2/Rapsyn interaction.
authors.affiliation: From the Institut für Biochemie, Friedrich-Alexander Universität Erlangen-Nürnberg, Fahrstrasse 17, D-91054 Erlangen, Germany.
authors.forename: Dustin
authors.initials: D
authors.lastname: Herrmann
authors.affiliation: From the Institut für Biochemie, Friedrich-Alexander Universität Erlangen-Nürnberg, Fahrstrasse 17, D-91054 Erlangen, Germany.
authors.forename: Marion
authors.initials: M
authors.lastname: Straubinger
authors.affiliation: From the Institut für Biochemie, Friedrich-Alexander Universität Erlangen-Nürnberg, Fahrstrasse 17, D-91054 Erlangen, Germany said.hashemolhosseini@fau.de.
authors.forename: Said
authors.initials: S
authors.lastname: Hashemolhosseini
mesh_terms: D048948:14-3-3 Proteins / Q000235:genetics / Q000378:metabolism*; D000818:Animals; D047390:Casein Kinase II / Q000235:genetics / Q000378:metabolism*; D018604:Epitope Mapping; D000939:Epitopes / Q000235:genetics / Q000378:metabolism; D057809:HEK293 Cells; D006801:Humans; D051379:Mice; D009124:Muscle Proteins / Q000235:genetics / Q000378:metabolism*; D020125:Mutation, Missense; D009469:Neuromuscular Junction / Q000235:genetics / Q000378:metabolism*; D009479:Neuropeptides / Q000235:genetics / Q000378:metabolism*; D010766:Phosphorylation / Q000502:physiology; D020830:rac1 GTP-Binding Protein / Q000235:genetics / Q000378:metabolism*
chemical_list: D048948:14-3-3 Proteins; C511694:Dok-7 protein, mouse; D000939:Epitopes; D009124:Muscle Proteins; D009479:Neuropeptides; C484602:Rac1 protein, mouse; C051609:peripheral membrane protein 43K; D047390:Casein Kinase II; D020830:rac1 GTP-Binding Protein
keywords: 14-3-3 protein; CK2; Dok-7; Rac (Rac GTPase); neuromuscular junction; protein kinase; protein-protein interaction; rapsyn; synapse