Phosphorylation of the carboxyl terminal region of dystrophin by mitogen-activated protein (MAP) kinase |
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Authors: | Carrie S Shemanko Jasbinder S Sanghera Rachel E Milner Steven Pelech Marek Michalak |
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Institution: | (1) MRC Group in Molecular Biology of Membrane, Department of Biochemistry, University of Alberta, 424 Heritage Medical Research Center, T6G 2S2 Edmonton, Alberta, Canada;(2) Biomedical Research Centre, University of British Columbia, V6T 1Z3 Vancouver, British Columbia, Canada;(3) Kinetek Biotechnology Corporation, Suite 500-220 W. 6th Avenue, V5Z 1A1 Vancouver, British Columbia, Canada |
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Abstract: | Dystrophin is the 427-kDa protein product of the Duchenne muscular dystrophy gene (DMD). The function of this protein remains to be elucidated. We have recently reported that dystrophin is phosphorylated,in vivo, in rat skeletal muscle primary cell culture (RE Milner, JL Busaan, CFB Holmes, JH Wang, M Michalak (1993) J Biol Chem 268: 21901–21905). This observation suggests that protein phosphorylation may have some role in modulating the function of dystrophin or its interaction with membrane associate dystroglycan. We report here that the carboxyl-terminal of dystrophin is phosphorylated by the MAP kinase p44mpk (mitogen-activated protein kinase), from the sea star oocytes and by soluble extracts of rabbit skeletal muscle. Importantly we showed that native dystrophin in isolated sarcolemmal vesicles is phosphorylated by sea star p44mpk. Partial purification and immunological analysis show that a mammalian kinase related to p44mpk is present in the skeletal muscle extracts and that it contributes to phosphorylation of the carboxyl-terminal of dystrophin. This kinase phosphorylates dystrophin on a threonine residue(s). We conclude that phosphorylation of dystrophin may play an important role in the function of this cytoskeletal protein.Abbreviations MAP kinase
mitogen-activated protein kinase
- DMD
Duchenne muscular dystrophy
- GST
Glutathione S-transferase
- PAGE
polyacrylamide gel electrophoresis
- EDTA
ethylenediaminetetraacetic acid
- EGTA
ethylene glycol bis(-aminoethyl ether)-N,N,N,N-tetraacetic acid
- MOPS
4-morpholinepropanesulfonic acid |
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Keywords: | dystrophin protein kinase protein phosphorylation Duchenne muscular dystrophy |
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