The interaction of dystrophin with beta-dystroglycan is regulated by tyrosine phosphorylation

Dystrophin and the dystrophin-associated protein complex (DA-PC) have recen tly been implicated in cell signalling events. These proteins are ideally p laced to transduce signals from the extracellular matrix (ECM) to the cytos keleton. Here we show that beta -dystroglycan is tyrosine-phosphorylated in C2/C4 mouse myotubes. Tyrosine phosphorylation was detected by mobility sh ifts on SDS-polyacrylamide gels (SDS-PAGE) and confirmed by immunoprecipita tion and two-dimensional gel electrophoresis. The potential functional sign ificance of this tyrosine phosphorylation was investigated using peptide 'S POTs' assays. Phosphorylation of tyrosine in the 15 most C-terminal amino a cids of beta -dystroglycan disrupts its interaction with dystrophin. The ty rosine residue in beta -dystroglycan's WW-binding motif PPPY appears to be the most crucial in disrupting the beta -dystroglycan-dystrophin interactio n. beta -dystroglycan forms the essential link between dystrophin and the r est of the DAPC. This regulation by tyrosine phosphorylation may have impli cations in the pathogenesis and treatment of Duchenne's muscular dystrophy (DMD). (C) 2001 Elsevier Science Inc. All rights reserved.