SH3 domain-mediated interaction of dystroglycan and Grb2.
Dystroglycan is a novel laminin receptor that links the extracellular matrix and sarcolemma in skeletal muscle. The dystroglycan complex containing alpha- and beta-dystroglycan also serves as an agrin receptor in muscle, where it may regulate agrin-induced acetylcholine receptor clustering at the neuromuscular junction. beta-Dystroglycan has now been expressed in vitro and shown to directly interact with Grb2, an adapter protein involved in signal transduction and cytoskeletal organization. Protein binding assays with two Grb2 mutants, Grb2/P49L and Grb2/G203R, which correspond to the loss-of-function mutants in the Caenorhabditis elegans sem-5, demonstrated that the dystroglycan-Grb2 association is through beta-dystroglycan C-terminal proline-rich domains and Grb2 Src homology 3 domains. Affinity chromatography has also shown endogenous skeletal muscle Grb2 interacts with beta-dystroglycan. Immunoprecipitation experiments have demonstrated that Grb2 associates with alpha/beta-dystroglycan in vivo in both skeletal muscle and brain. The specific dystroglycan-Grb2 interaction may play an important role in extracellular matrix-mediated signal transduction and/or cytoskeleton organization in skeletal muscle that may be essential for muscle cell viability.
Yang
B
B
Howard Hughes Medical Institute, College of Medicine, Iowa City, Iowa, USA.
Jung
D
D
Motto
D
D
Meyer
J
J
Koretzky
G
G
Campbell
K P
KP
D048868:Adaptor Proteins, Signal Transducing; D000818:Animals; D001483:Base Sequence; D001665:Binding Sites; D017173:Caenorhabditis elegans / Q000235:genetics; D003598:Cytoskeletal Proteins / Q000737:chemistry / Q000378:metabolism*; D018076:DNA, Complementary / Q000235:genetics; D049030:Dystroglycans; D016326:Extracellular Matrix Proteins / Q000502:physiology; D051380:GRB2 Adaptor Protein; D015801:Helminth Proteins / Q000235:genetics; D008562:Membrane Glycoproteins / Q000737:chemistry / Q000378:metabolism*; D008969:Molecular Sequence Data; D009124:Muscle Proteins / Q000378:metabolism; D011485:Protein Binding; D017434:Protein Structure, Tertiary; D011506:Proteins / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D011817:Rabbits; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D015398:Signal Transduction
D048868:Adaptor Proteins, Signal Transducing; D003598:Cytoskeletal Proteins; D018076:DNA, Complementary; D016326:Extracellular Matrix Proteins; D051380:GRB2 Adaptor Protein; D015801:Helminth Proteins; D008562:Membrane Glycoproteins; D009124:Muscle Proteins; D011506:Proteins; D011993:Recombinant Fusion Proteins; D049030:Dystroglycans