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Increased contractility in transgenic mice with overexpression of the targeting subunit B56a of PP2A
Author(s) -
Kirchhefer Uwe,
Boknik P.,
Heinick A.,
Kucerova D.,
Neumann J.,
Schmitz W.,
Stümpel F.,
Müller F. U.
Publication year - 2011
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fasebj.25.1_supplement.1013.2
Subject(s) - protein phosphatase 2 , protein subunit , chemistry , contractility , heterotrimeric g protein , okadaic acid , medicine , endocrinology , phosphatase , microbiology and biotechnology , biology , biochemistry , g protein , enzyme , receptor , gene
Protein phosphatase (PP2A) is a heterotrimeric protein consisting of a catalytic (C), a scaffolding (A), and a regulatory (B) subunit. The B subunit anchors the C subunit to subcellular locations and therefore defines, at least in part, substrate specificity. To reveal new insights in the regulation of the main cardiac B subunit, we generated transgenic mice with heart‐directed overexpression of human B56α under the control of the α‐MHC promoter (TG). TG hearts exhibited a 2‐fold overexpression of B56α compared to wild‐type (WT) mice. This was associated with a 2‐fold higher protein expression of C (n=5, P <0.05). Consistently, total phosphorylase a ‐PP activity was increased by 25% in TG (n=5, P <0.05). Overexpression of B56α reduced the efficacy of PP2A inhibition by okadaic acid (OA), a PP2A selective PP inhibitor, at low concentrations. The application of 0.3 nmol/L OA decreased total PP activity by 18% and 33% in TG and WT, respectively (n=5, P <0.05). The protein expression of Aα remained unchanged between TG and WT, as observed for PP1‐C. Force of contraction was increased after application of 10 μmol/L isoproterenol by 63% in TG compared to WT isolated left atria (n=6, P <0.05). We conclude that overexpression of B56α led to a higher contractility in TG after β‐adrenergic stimulation. Thus, our data suggest a critical role of PP2A targeting by B56α in the regulation of cardiac contractile function. This study was supported by the DFG and the IMF Münster.