Localization of myotonic dystrophy protein kinase in skeletal muscle and its alteration with disease.
Myotonic dystrophy (DM) is an autosomal dominant disorder which affects skeletal muscle, heart, eye lens, brain, and endocrine functions. The disease-causing mutations are expansions of the triplet repeat CTG in the 3' untranslated region of a locus which encodes a serine/threonine protein kinase that represents a new family of protein kinases. A monoclonal antibody to a recombinant DM protein kinase (mAb DM-1) reacts specifically with the 64 kDa isoform of DM protein kinase in type I fibers in skeletal muscle, the fiber type which characteristically atrophies in the disease. Within type I fibers of normal muscle the isoform may be localized with mAb DM-1 to the triad region. In the DM disease state, the enzyme is redistributed to the pathologically characteristic peripheral sarcoplasmic masses. In markedly affected human distal myotonic muscle, the levels of the 64 kDa DM kinase isoform are elevated relative to slow skeletal myosin heavy chain. These results suggest that, consistent with the dominant clinical phenotype, the localization and accumulation of the 64 kDa isoform are altered in the heterozygous disease state.
Dunne
P W
PW
Department of Neurology, Baylor College of Medicine, Houston, TX 77030, USA.
Ma
L
L
Casey
D L
DL
Harati
Y
Y
Epstein
H F
HF
D000180:Acrylic Resins / Q000378:metabolism; D000328:Adult; D000818:Animals; D001665:Binding Sites; D002460:Cell Line; D004591:Electrophoresis, Polyacrylamide Gel; D005260:Female; D006801:Humans; D007527:Isoenzymes / Q000378:metabolism*; D008297:Male; D051379:Mice; D008807:Mice, Inbred BALB C; D008875:Middle Aged; D018657:Muscle Fibers, Slow-Twitch / Q000378:metabolism; D018482:Muscle, Skeletal / Q000378:metabolism* / Q000473:pathology; D009223:Myotonic Dystrophy / Q000201:enzymology* / Q000473:pathology; D065636:Myotonin-Protein Kinase; D010766:Phosphorylation; D017346:Protein Serine-Threonine Kinases / Q000378:metabolism*; D051381:Rats; D017207:Rats, Sprague-Dawley; D011993:Recombinant Fusion Proteins / Q000378:metabolism; D012508:Sarcolemma / Q000378:metabolism
D000180:Acrylic Resins; C585517:DMPK protein, human; C585516:DMPK protein, mouse; D007527:Isoenzymes; D011993:Recombinant Fusion Proteins; C060386:Triad resin; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases