ArticleThe Journal of biological chemistry2010
Distinct sarcomeric substrates are responsible for protein kinase D-mediated regulation of cardiac myofilament Ca2+ sensitivity and cross-bridge cycling.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 99 citations in OpenAlex.
- Cardiac myosin binding protein-C phosphorylation as a function of multiple protein kinase and phosphatase activities.Nature communications · 2024Article
- The mechanism of 25-hydroxycholesterol-mediated suppression of atrial β1-adrenergic responses.Pflugers Archiv : European journal of physiology · 2024Article
- Protein Kinase D Plays a Crucial Role in Maintaining Cardiac Homeostasis by Regulating Post-Translational Modifications of Myofilament Proteins.International journal of molecular sciences · 2024Article
- Cardiac Protein Kinase D1 ablation alters the myocytes β-adrenergic response.Journal of molecular and cellular cardiology · 2023Article
- Etiology of genetic muscle disorders induced by mutations in fast and slow skeletal MyBP-C paralogs.Experimental & molecular medicine · 2023Review
- Article
- Decoding the Cardiac Actions of Protein Kinase D Isoforms.Molecular pharmacology · 2021Review
- Receptor-independent modulation of cAMP-dependent protein kinase and protein phosphatase signaling in cardiac myocytes by oxidizing agents.The Journal of biological chemistry · 2020Article
- High efficiency preparation of skinned mouse cardiac muscle strips from cryosections for contractility studies.Experimental physiology · 2020Article
- Heart Failure in Humans Reduces Contractile Force in Myocardium From Both Ventricles.JACC. Basic to translational science · 2020Article
- MyBP-C: one protein to govern them all.Journal of muscle research and cell motility · 2020Review
- Pressure Overload Is Associated With Low Levels of Troponin I and Myosin Binding Protein C Phosphorylation in the Hearts of Patients With Aortic Stenosis.Frontiers in physiology · 2020Article
- Human cardiac myosin-binding protein C restricts actin structural dynamics in a cooperative and phosphorylation-sensitive manner.The Journal of biological chemistry · 2019Article
- Site-specific phosphorylation of myosin binding protein-C coordinates thin and thick filament activation in cardiac muscle.Proceedings of the National Academy of Sciences of the United States of America · 2019Article
- Structural and functional effects of myosin-binding protein-C phosphorylation in heart muscle are not mimicked by serine-to-aspartate substitutions.The Journal of biological chemistry · 2018Article
- Monophosphorylation of cardiac troponin-I at Ser-23/24 is sufficient to regulate cardiac myofibrillar CaThe Journal of biological chemistry · 2018Article
- Thick Filament Protein Network, Functions, and Disease Association.Comprehensive Physiology · 2018Review
- β-Adrenergic regulation of cardiac type 2A protein phosphatase through phosphorylation of regulatory subunit B56δ at S573.Journal of molecular and cellular cardiology · 2018Article
- Hypertrophic cardiomyopathy and the myosin mesa: viewing an old disease in a new light.Biophysical reviews · 2018Review
- Acute and Chronic Effects of Protein Kinase-D Signaling on Cardiac Energy Metabolism.Frontiers in cardiovascular medicine · 2018Review
17 more citing papers are in PubMed but not listed here.
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Authors and funding
9 authors at 3 institutions in 2 countries.
Funding
Abstract
Protein kinase D (PKD), a serine/threonine kinase with emerging cardiovascular functions, phosphorylates cardiac troponin I (cTnI) at Ser(22)/Ser(23), reduces myofilament Ca(2+) sensitivity, and accelerates cross-bridge cycle kinetics. Whether PKD regulates cardiac myofilament function entirely through cTnI phosphorylation at Ser(22)/Ser(23) remains to be established. To determine the role of cTnI phosphorylation at Ser(22)/Ser(23) in PKD-mediated regulation of cardiac myofilament function, we used transgenic mice that express cTnI in which Ser(22)/Ser(23) are substituted by nonphosphorylatable Ala (cTnI-Ala(2)). In skinned myocardium from wild-type (WT) mice, PKD increased cTnI phosphorylation at Ser(22)/Ser(23) and decreased the Ca(2+) sensitivity of force. In contrast, PKD had no effect on the Ca(2+) sensitivity of force in myocardium from cTnI-Ala(2) mice, in which Ser(22)/Ser(23) were unavailable for phosphorylation. Surprisingly, PKD accelerated cross-bridge cycle kinetics similarly in myocardium from WT and cTnI-Ala(2) mice. Because cardiac myosin-binding protein C (cMyBP-C) phosphorylation underlies cAMP-dependent protein kinase (PKA)-mediated acceleration of cross-bridge cycle kinetics, we explored whether PKD phosphorylates cMyBP-C at its PKA sites, using recombinant C1C2 fragments with or without site-specific Ser/Ala substitutions. Kinase assays confirmed that PKA phosphorylates Ser(273), Ser(282), and Ser(302), and revealed that PKD phosphorylates only Ser(302). Furthermore, PKD phosphorylated Ser(302) selectively and to a similar extent in native cMyBP-C of skinned myocardium from WT and cTnI-Ala(2) mice, and this phosphorylation occurred throughout the C-zones of sarcomeric A-bands. In conclusion, PKD reduces myofilament Ca(2+) sensitivity through cTnI phosphorylation at Ser(22)/Ser(23) but accelerates cross-bridge cycle kinetics by a distinct mechanism. PKD phosphorylates cMyBP-C at Ser(302), which may mediate the latter effect.
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