The interaction of dystrophin with beta-dystroglycan is regulated by tyrosine phosphorylation.
Dystrophin and the dystrophin-associated protein complex (DAPC) have recently been implicated in cell signalling events. These proteins are ideally placed to transduce signals from the extracellular matrix (ECM) to the cytoskeleton. Here we show that beta-dystroglycan is tyrosine-phosphorylated in C2/C4 mouse myotubes. Tyrosine phosphorylation was detected by mobility shifts on SDS-polyacrylamide gels (SDS-PAGE) and confirmed by immunoprecipitation and two-dimensional gel electrophoresis. The potential functional significance of this tyrosine phosphorylation was investigated using peptide 'SPOTs' assays. Phosphorylation of tyrosine in the 15 most C-terminal amino acids of beta-dystroglycan disrupts its interaction with dystrophin. The tyrosine residue in beta-dystroglycan's WW-binding motif PPPY appears to be the most crucial in disrupting the beta-dystroglycan-dystrophin interaction. beta-dystroglycan forms the essential link between dystrophin and the rest of the DAPC. This regulation by tyrosine phosphorylation may have implications in the pathogenesis and treatment of Duchenne's muscular dystrophy (DMD).
Ilsley
J L
JL
Institute of Cell and Molecular Biology, University of Edinburgh, King's Buildings, Mayfield Road, Edinburgh, Scotland EH9 3JR, UK.
Sudol
M
M
Winder
S J
SJ
D020816:Amino Acid Motifs; D000595:Amino Acid Sequence; D000818:Animals; D002454:Cell Differentiation; D002460:Cell Line; D003598:Cytoskeletal Proteins / Q000378:metabolism*; D049030:Dystroglycans; D016189:Dystrophin / Q000737:chemistry / Q000378:metabolism*; D008562:Membrane Glycoproteins / Q000378:metabolism*; D051379:Mice; D008958:Models, Molecular; D008969:Molecular Sequence Data; D024510:Muscle Development; D018482:Muscle, Skeletal / Q000166:cytology / Q000254:growth & development / Q000378:metabolism*; D010766:Phosphorylation; D019000:Phosphotyrosine / Q000378:metabolism; D011485:Protein Binding
D003598:Cytoskeletal Proteins; D016189:Dystrophin; D008562:Membrane Glycoproteins; D049030:Dystroglycans; D019000:Phosphotyrosine