IDENTIFICATION, TISSUE-SPECIFIC EXPRESSION, AND SUBCELLULAR-LOCALIZATION OF THE 80-KDA AND 71-KDA FORMS OF MYOTONIC-DYSTROPHY KINASE PROTEIN

The protein product of the myotonic dystrophy (DM) gene is a putative serine-threonine protein kinase (DM kinase). Previous reports have cha racterized the DM gene product as various 50-62-kDa proteins. The pred icted protein size from DM cDNA sequence is 69 kDa. We therefore expre ssed a full-length recombinant human DM kinase protein and compared it s size and expression to heart, cardiac Purkinje fibers, and skeletal muscle from normal and DM subjects. Recombinantly expressed DM kinase and endogenous DM kinase in human heart, displayed two immunoreactive DM kinase proteins with apparent molecular sizes of 71 and 80 kDa, sug gesting that these prior reports are incorrect. In cardiac Purkinje fi bers the 71-kDa protein was the major form, and in skeletal muscle the 80-kDa protein was the major form. Immunostaining showed DM kinase lo calized to neuromuscular junctions in skeletal muscle and intercalated discs in heart and Purkinje fibers. DM subjects showed low abundance of DM kinase in heart and skeletal muscle, suggesting haplotype insuff iciency as a potential mechanism for disease expression. These studies describe differential expression of two protein forms of DM kinase, w hich are localized to specialized cellular structures associated with impulse transmission.