Protein kinase CK2 interacts at the neuromuscular synapse with Rapsyn, Rac1, 14-3-3{gamma} and Dok-7, and phosphorylates the latter two [Signal Transduction]

July 21st, 2015 by Herrmann, D., Straubinger, M., Hashemolhosseini, S.

Previously, we demonstrated that the protein kinase CK2 associates with and phosphorylates the receptor tyrosine kinase MuSK at the neuromuscular junction (NMJ), thereby preventing fragmentation of the NMJs [Cheusova et al, Genes & Development, 2006]. 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) weakly the α and β subunits of the nicotinic acetylcholine receptors (AChR), (b) dishevelled (dsh), and (c) another four proteins with strong interaction: Rapsyn, Rac1, 14-3-3γ and Dok-7. It turned out that CK2 phosphorylates 14-3-3γ at serine residue 235 and Dok-7 at several serine residues, but neither Rapsyn nor Rac1. Further, phosphomimetic Dok-7 mutants aggregate AChRs in C2C12 myotubes with significantly higher frequency than wildtype Dok-7. Additionally, we mapped the interacting epitopes of all four binding partners to CK2 and gained thereby insights to surmise on the potential role of the CK2 - Rapsyn interaction.
  • Posted in Journal of Biological Chemistry, Publications
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