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• W4286512656 endingPage "102296" @default.
• W4286512656 startingPage "102296" @default.
• W4286512656 abstract "Cardiac muscle myosin regulatory light chain (RLC) is constitutively phosphorylated at ∼0.4 mol phosphate/mol RLC in normal hearts, and phosphorylation is maintained by balanced activities of dedicated cardiac muscle-specific myosin light chain kinase and myosin light chain phosphatase (MLCP). Previously, the identity of the cardiac-MLCP was biochemically shown to be similar to the smooth muscle MLCP, which is a well-characterized trimeric protein comprising the regulatory subunit (MYPT1), catalytic subunit PP1cβ, and accessory subunit M20. In smooth muscles in vivo, MYPT1 and PP1cβ co-stabilize each other and are both necessary for normal smooth muscle contractions. In the cardiac muscle, MYPT1 and MYPT2 are both expressed, but contributions to physiological regulation of cardiac myosin dephosphorylation are unclear. We hypothesized that the main catalytic subunit for cardiac-MLCP is PP1cβ, and maintenance of RLC phosphorylation in vivo is dependent on regulation by striated muscle-specific MYPT2. Here, we used PP1cβ conditional knockout mice to biochemically define cardiac-MLCP proteins and developed a cardiac myofibrillar phosphatase assay to measure the direct contribution of MYPT-regulated and MYPT-independent phosphatase activities toward phosphorylated cardiac myosin. We report that (1) PP1cβ is the main isoform expressed in the cardiac myocyte, (2) cardiac muscle pathogenesis in PP1cβ knockout animals involve upregulation of total PP1cα in myocytes and non-muscle cells, (3) the stability of cardiac MYPT1 and MYPT2 proteins in vivo is not dependent on the PP1cβ expression, and (4) phosphorylated myofibrillar cardiac myosin is dephosphorylated by both myosin-targeted and soluble MYPT-independent PP1cβ activities. These results contribute to our understanding of the cardiac-MLCP in vivo." @default.
• W4286512656 created "2022-07-22" @default.
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• W4286512656 date "2022-09-01" @default.
• W4286512656 modified "2023-10-16" @default.
• W4286512656 title "Myosin light chain phosphatase catalytic subunit dephosphorylates cardiac myosin via mechanisms dependent and independent of the MYPT regulatory subunits" @default.
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• W4286512656 doi "https://doi.org/10.1016/j.jbc.2022.102296" @default.
• W4286512656 hasPubMedId "https://pubmed.ncbi.nlm.nih.gov/35872014" @default.
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