Myotonin-protein kinase (MT-PK) also known as myotonic dystrophy protein kinase (MDPK) or dystrophia myotonica protein kinase (DMPK) is an enzyme that in humans is encoded by the DMPK gene.[5][6][7]
The DMPK gene product is a Ser/Thr protein kinase homologous to the MRCK p21-activated kinases and Rho kinase family.[8] Data obtained by using antibodies that detect specific isoforms of DMPK indicate that the most abundant isoform of DMPK is an 80-kDa protein expressed almost exclusively in smooth, skeletal, and cardiac muscles.[9] This kinase exists both as a membrane-associated and as a soluble form in human left ventricular samples. The different C termini of DMPK that arise from alternative splicing determine its localization to the endoplasmic reticulum, mitochondria, or cytosol in transfected COS-1 cells.[10] Among the substrates for DMPK proposed by in vitro studies are phospholemman, the dihydropyridine receptor, and the myosin phosphatase targeting subunit. However, an in vivo demonstration of the phosphorylation of these substrates by DMPK remains to be established, and a link between these substrates and the clinical manifestations of myotonic dystrophy (DM) is unclear.[11][12]
- ^ a b c GRCh38: Ensembl release 89: ENSG00000104936 – Ensembl, May 2017
- ^ a b c GRCm38: Ensembl release 89: ENSMUSG00000030409 – Ensembl, May 2017
- ^ "Human PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ "Mouse PubMed Reference:". National Center for Biotechnology Information, U.S. National Library of Medicine.
- ^ Mahadevan M, Tsilfidis C, Sabourin L, Shutler G, Amemiya C, Jansen G, Neville C, Narang M, Barceló J, O'Hoy K (March 1992). "Myotonic dystrophy mutation: an unstable CTG repeat in the 3' untranslated region of the gene". Science. 255 (5049): 1253–5. Bibcode:1992Sci...255.1253M. doi:10.1126/science.1546325. PMID 1546325.
- ^ Fu YH, Pizzuti A, Fenwick RG, King J, Rajnarayan S, Dunne PW, Dubel J, Nasser GA, Ashizawa T, de Jong P (March 1992). "An unstable triplet repeat in a gene related to myotonic muscular dystrophy". Science. 255 (5049): 1256–8. Bibcode:1992Sci...255.1256F. doi:10.1126/science.1546326. PMID 1546326.
- ^ Cite error: The named reference
entrezwas invoked but never defined (see the help page). - ^ Amano M, Chihara K, Nakamura N, Kaneko T, Matsuura Y, Kaibuchi K (November 1999). "The COOH terminus of Rho-kinase negatively regulates rho-kinase activity". The Journal of Biological Chemistry. 274 (45): 32418–24. doi:10.1074/jbc.274.45.32418. PMID 10542285.
- ^ Lam LT, Pham YC, Nguyen TM, Morris GE (September 2000). "Characterization of a monoclonal antibody panel shows that the myotonic dystrophy protein kinase, DMPK, is expressed almost exclusively in muscle and heart". Human Molecular Genetics. 9 (14): 2167–73. doi:10.1093/hmg/9.14.2167. PMID 10958655.
- ^ Wansink DG, van Herpen RE, Coerwinkel-Driessen MM, Groenen PJ, Hemmings BA, Wieringa B (August 2003). "Alternative splicing controls myotonic dystrophy protein kinase structure, enzymatic activity, and subcellular localization". Molecular and Cellular Biology. 23 (16): 5489–501. doi:10.1128/mcb.23.16.5489-5501.2003. PMC 166319. PMID 12897125.
- ^ Timchenko L, Nastainczyk W, Schneider T, Patel B, Hofmann F, Caskey CT (June 1995). "Full-length myotonin protein kinase (72 kDa) displays serine kinase activity". Proceedings of the National Academy of Sciences of the United States of America. 92 (12): 5366–70. Bibcode:1995PNAS...92.5366T. doi:10.1073/pnas.92.12.5366. PMC 41695. PMID 7777513.
- ^ Kaliman P, Catalucci D, Lam JT, Kondo R, Gutiérrez JC, Reddy S, Palacín M, Zorzano A, Chien KR, Ruiz-Lozano P (March 2005). "Myotonic dystrophy protein kinase phosphorylates phospholamban and regulates calcium uptake in cardiomyocyte sarcoplasmic reticulum". The Journal of Biological Chemistry. 280 (9): 8016–21. doi:10.1074/jbc.M412845200. PMID 15598648.