[Physiological function of myotonin protein kinase].
The mutation underlying myotonic dystrophy is the expansion of polymorphic CTG repeat in the 3'-noncoding region of the myotonin protein kinase (MtPK) gene mapping to chromosome 19q13.3. A full-length cDNA of human MtPK was cloned and expressed in COS-1 cells. We purified native full-length MtPK from rat skeletal muscle. This 70 kDa MtPK is localized in sarcoplasmic reticulum fraction, whereas the previously reported 55 kDa protein was observed in nuclear extract or the sarcoplasmic reticulum membrane. Based on the cDNA sequence, human MtPK was previously reported to have two amino acid sequence variations at the C-terminus, one GAARAP (RAP type) and PALPEP (PEP type). The MtPK purified appeared to be almost entirely RAP type. Stable expression of MtPK in mouse C2C12 cells caused the activation of chloride efflux. Expansion of CTG repeats suppressed myogenic differentiation. Collectively, the results indicate that prolonged MtPK activation provides a link between intracellular signal transduction pathway and membrane permeability.
Ishiura
S
S
Institute of Molecular and Cellular Biosciences, University of Tokyo.
D000818:Animals; D019556:COS Cells; D002454:Cell Differentiation; D002463:Cell Membrane Permeability; D002522:Chlorocebus aethiops; D002888:Chromosomes, Human, Pair 19; D006801:Humans; D051379:Mice; D009132:Muscles / Q000166:cytology; D009154:Mutation; D009223:Myotonic Dystrophy / Q000209:etiology; D065636:Myotonin-Protein Kinase; D011494:Protein Kinases / Q000737:chemistry / Q000502:physiology*; D017346:Protein Serine-Threonine Kinases; D051381:Rats; D015398:Signal Transduction; D018911:Trinucleotide Repeats
C585517:DMPK protein, human; C585516:DMPK protein, mouse; D011494:Protein Kinases; D065636:Myotonin-Protein Kinase; D017346:Protein Serine-Threonine Kinases