Examination of transcript amounts and activity of protein kinase CK2 in muscle lysates of different types of human muscle pathologies
- 115 Downloads
Motoneurons release the heparansulfate proteoglycan agrin and thereby activate the muscle-specific receptor tyrosine kinase (MuSK), which is the main organizer of subsynaptic specializations at the neuromuscular junction. Recently, we showed that (1) the protein kinase CK2 interacts with the intracellular region of MuSK; (2) the CK2 protein is enriched and co-localized with MuSK at postsynaptic specializations; (3) CK2-mediated phosphorylation of serine residues within a specific MuSK epitope, named the kinase insert, regulates acetylcholine receptor (AChR) clustering; (4) muscle-specific CK2β knockout mice develop a myasthenic phenotype due to impaired muscle endplate structure and function (see Genes Dev 20(13):1800–1816, 2006). Here, we investigated for the first time if CK2 is modulated in biopsies from human patients. To this end, we measured transcript amounts of the subunits CK2α and CK2β and determined holoenzyme CK2 activity in 34 muscle biopsies of human patients with different muscle pathologies.
KeywordsProtein kinase CK2 Skeletal muscle Myopathy Myasthenia
We are indebted to Clarke Slater (NewCastle, England) for critically reading the manuscript and numerous helpful comments. This work was supported by grants of the Interdisciplinary Center for Clinical Research at the University Hospital of the University of Erlangen-Nuremberg (IZKF E2) to Dieter Heuss and Said Hashemolhosseini and the Deutsche Forschungsgemeinschaft (DFG) to Said Hashemolhosseini (HA 3309/1-3).
- 9.Sadasivam G, Willmann R, Lin S, Erb-Vogtli S, Kong XC, Ruegg MA et al (2005) Src-family kinases stabilize the neuromuscular synapse in vivo via protein interactions, phosphorylation, and cytoskeletal linkage of acetylcholine receptors. J Neurosci 25:10479–10493. doi: 10.1523/JNEUROSCI.2103-05.2005 PubMedCrossRefGoogle Scholar
- 19.Slater CR (2007) Structural factors influencing the efficacy of neuromuscular transmission. Ann NY Acad Sci. Dec 20Google Scholar