Phospholemman is a substrate for myotonic dystrophy protein kinase

J. Paul Mounsey, J. Edward John, Steve M. Helmke, Erik W. Bush, John Gilbert, Allen D. Roses, M. Benjamin Perryman, Larry Jones, J. Randall Moorman

Research output: Contribution to journalArticle

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Abstract

The genetic abnormality in myotonic muscular dystrophy, multiple CTG repeats lie upstream of a gene that encodes a novel protein kinase, myotonic dystrophy protein kinase (DMPK). Phospholemman (PLM), a major membrane substrate for phosphorylation by protein kinases A and C, induces Cl currents (I(Cl(PLM))) when expressed in Xenopus oocytes. To test the idea that PLM is a substrate for DMPK, we measured in vitro phosphorylation of purified PLM by DMPK. To assess the functional effects of PLM phosphorylation we compared I(Cl(PLM)) in Xenopus oocytes expressing PLM alone to currents in oocytes co-expressing DMPK, and examined the effect of DMPK on oocyte membrane PLM expression. We found that PLM is indeed a good substrate for DMPK in vitro. Co-expression of DMPK with PLM in oocytes resulted in a reduction in I(Cl(PLM)). This was most likely a specific effect of phosphorylation of PLM by DMPK, as the effect was not present in oocytes expressing a phos(-) PLM mutant in which all potential phosphorylation had been disabled by Ser → Ala substitution. The biophysical characteristics of I(Cl(PLM)) were not changed by DMPK or by the phos(-) mutation. Co-expression of DMPK reduced the expression of PLM in oocyte membranes, suggesting a possible mechanism for the observed reduction in I(Cl(PLM)) amplitude. These data show that PLM is a substrate for phosphorylation by DMPK and provide functional evidence for modulation of PLM function by phosphorylation.

Original languageEnglish
Pages (from-to)23362-23367
Number of pages6
JournalJournal of Biological Chemistry
Volume275
Issue number30
DOIs
StatePublished - Jul 28 2000

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Substrates
Phosphorylation
Oocytes
phospholemman
Myotonin-Protein Kinase
Xenopus
Membranes
Myotonic Dystrophy
Muscular Dystrophies
Cyclic AMP-Dependent Protein Kinases
Protein Kinases
Protein Kinase C
Substitution reactions
Genes
Modulation
Proteins
Mutation

ASJC Scopus subject areas

  • Biochemistry

Cite this

Mounsey, J. P., John, J. E., Helmke, S. M., Bush, E. W., Gilbert, J., Roses, A. D., ... Moorman, J. R. (2000). Phospholemman is a substrate for myotonic dystrophy protein kinase. Journal of Biological Chemistry, 275(30), 23362-23367. https://doi.org/10.1074/jbc.M000899200

Phospholemman is a substrate for myotonic dystrophy protein kinase. / Mounsey, J. Paul; John, J. Edward; Helmke, Steve M.; Bush, Erik W.; Gilbert, John; Roses, Allen D.; Perryman, M. Benjamin; Jones, Larry; Moorman, J. Randall.

In: Journal of Biological Chemistry, Vol. 275, No. 30, 28.07.2000, p. 23362-23367.

Research output: Contribution to journalArticle

Mounsey, JP, John, JE, Helmke, SM, Bush, EW, Gilbert, J, Roses, AD, Perryman, MB, Jones, L & Moorman, JR 2000, 'Phospholemman is a substrate for myotonic dystrophy protein kinase', Journal of Biological Chemistry, vol. 275, no. 30, pp. 23362-23367. https://doi.org/10.1074/jbc.M000899200
Mounsey JP, John JE, Helmke SM, Bush EW, Gilbert J, Roses AD et al. Phospholemman is a substrate for myotonic dystrophy protein kinase. Journal of Biological Chemistry. 2000 Jul 28;275(30):23362-23367. https://doi.org/10.1074/jbc.M000899200
Mounsey, J. Paul ; John, J. Edward ; Helmke, Steve M. ; Bush, Erik W. ; Gilbert, John ; Roses, Allen D. ; Perryman, M. Benjamin ; Jones, Larry ; Moorman, J. Randall. / Phospholemman is a substrate for myotonic dystrophy protein kinase. In: Journal of Biological Chemistry. 2000 ; Vol. 275, No. 30. pp. 23362-23367.
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