Medizinische Universität Graz Austria/Österreich - Forschungsportal - Medical University of Graz
Gewählte Publikation:
Brittsan, AG; Carr, AN; Schmidt, AG; Kranias, EG.
Maximal inhibition of SERCA2 Ca(2+) affinity by phospholamban in transgenic hearts overexpressing a non-phosphorylatable form of phospholamban.
J Biol Chem. 2000; 275(16): 12129-12135.
Doi: 10.1074/jbc.275.16.12129
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- Co-Autor*innen der Med Uni Graz
- Schmidt Albrecht
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- Abstract:
- Phospholamban is a phosphoprotein in the cardiac sarcoplasmic reticulum (SR) which regulates the apparent Ca(2+) affinity of the SR Ca(2+)-ATPase (SERCA2). To determine the levels of phospholamban which are associated with maximal inhibition of SERCA2, several lines of transgenic mice were generated which expressed increasing levels of a non-phosphorylatable form of phospholamban (S16A,T17A) specifically in the heart. This mutant form of phospholamban was chosen to prevent phosphorylation as a compensatory mechanism in vivo. Quantitative immunoblotting revealed increased phospholamban protein levels of 1.8-, 2.6-, 3.7-, and 4.7-fold in transgenic hearts compared with wild types. There were no changes in the expression levels of SERCA2, calsequestrin, calreticulin, and ryanodine receptor. Assessment of SR Ca(2+) uptake in hearts of transgenic mice indicated increases in the inhibition of the affinity of SERCA2 for Ca(2+) with increased phospholamban expression. Maximal inhibition was obtained at phospholamban expression levels of 2.6-fold or higher. Transgenic hearts with functional saturation in phospholamban:SERCA2 (>/=2.6:1) exhibited increases in beta-myosin heavy chain expression, associated with cardiac hypertrophy. These findings demonstrate that overexpression of a non-phosphorylatable form of phospholamban in transgenic mouse hearts resulted in saturation of the functional phospholamban:SERCA2 ratio at 2.6:1 and suggest that approximately 40% of the SR Ca(2+) pumps are functionally regulated by phospholamban in vivo.
- Find related publications in this database (using NLM MeSH Indexing)
- Animals -
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- Calcium - metabolism
- Calcium-Binding Proteins - metabolism Calcium-Binding Proteins - pharmacology
- Calcium-Transporting ATPases - metabolism
- Calreticulin -
- Calsequestrin - metabolism
- Heart - drug effects
- Kinetics -
- Mice -
- Mice, Transgenic -
- Mutagenesis, Site-Directed -
- Myocardium - metabolism
- Phosphorylation -
- Ribonucleoproteins - metabolism
- Ryanodine Receptor Calcium Release Channel - metabolism
- Sarcoplasmic Reticulum - metabolism