title: Phosphorylation of the carboxyl terminal region of dystrophin by mitogen-activated protein (MAP) kinase.
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.
authors.affiliation: Department of Biochemistry, University of Alberta, Edmonton, Canada.
authors.forename: C S
authors.initials: CS
authors.lastname: Shemanko
authors.forename: J S
authors.initials: JS
authors.lastname: Sanghera
authors.forename: R E
authors.initials: RE
authors.lastname: Milner
authors.forename: S
authors.initials: S
authors.lastname: Pelech
authors.forename: M
authors.initials: M
authors.lastname: Michalak
mesh_terms: D000818:Animals; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000378:metabolism*; D016189:Dystrophin / Q000378:metabolism*; D010766:Phosphorylation; D011817:Rabbits
chemical_list: D016189:Dystrophin; D017871:Calcium-Calmodulin-Dependent Protein Kinases