ArticleArchives of biochemistry and biophysics2014
Phosphorylation of protein kinase C sites Ser42/44 decreases Ca(2+)-sensitivity and blunts enhanced length-dependent activation in response to protein kinase A in human cardiomyocytes.
Article in Archives of biochemistry and biophysics, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 12 papers.
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Who cites it
12 citing papers in PubMed.
- Abnormal phosphorylation / dephosphorylation and CaHeart failure reviews · 2024Review
- Sarcomere length affects Ca2+ sensitivity of contraction in ischemic but not non-ischemic myocardium.The Journal of general physiology · 2023Article
- The interplay of inflammation, exosomes and CaCardiovascular diabetology · 2023Review
- The homozygous K280N troponin T mutation alters cross-bridge kinetics and energetics in human HCM.The Journal of general physiology · 2019Article
- The continuing evolution of cardiac troponin I biomarker analysis: from protein to proteoform.Expert review of proteomics · 2017Review
- Linking myofilaments to sudden cardiac death: recent advances.The Journal of physiology · 2017Review
- Functionally conservative substitutions at cardiac troponin I S43/45.Archives of biochemistry and biophysics · 2016Article
- Should we treat heart failure with phosphatase inhibitors? Better to start at the end.Journal of molecular and cellular cardiology · 2015Article
- A novel phosphorylation site, Serine 199, in the C-terminus of cardiac troponin I regulates calcium sensitivity and susceptibility to calpain-induced proteolysis.Journal of molecular and cellular cardiology · 2015Article
- Pathomechanisms in heart failure: the contractile connection.Journal of muscle research and cell motility · 2015Review
- The cardiac-specific N-terminal region of troponin I positions the regulatory domain of troponin C.Proceedings of the National Academy of Sciences of the United States of America · 2014Article
- Troponin I phosphorylation in human myocardium in health and disease.Netherlands heart journal : monthly journal of the Netherlands Society of Cardiology and the Netherlands Heart Foundation · 2014Article
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Authors and funding
8 authors.
Funding
Abstract
Protein kinase C (PKC)-mediated phosphorylation of troponin I (cTnI) at Ser42/44 is increased in heart failure. While studies in rodents demonstrated that PKC-mediated Ser42/44 phosphorylation decreases maximal force and ATPase activity, PKC incubation of human cardiomyocytes did not affect maximal force. We investigated whether Ser42/44 pseudo-phosphorylation affects force development and ATPase activity using troponin exchange in human myocardium. Additionally, we studied if pseudo-phosphorylated Ser42/44 modulates length-dependent activation of force, which is regulated by protein kinase A (PKA)-mediated cTnI-Ser23/24 phosphorylation. Isometric force was measured in membrane-permeabilized cardiomyocytes exchanged with human recombinant wild-type troponin or troponin mutated at Ser42/44 or Ser23/24 into aspartic acid (D) or alanine (A) to mimic phosphorylation and dephosphorylation, respectively. In troponin-exchanged donor cardiomyocytes experiments were repeated after PKA incubation. ATPase activity was measured in troponin-exchanged cardiac muscle strips. Compared to wild-type, 42D/44D decreased Ca(2+)-sensitivity without affecting maximal force in failing and donor cardiomyocytes. In donor myocardium, 42D/44D did not affect maximal ATPase activity or tension cost. Interestingly, 42D/44D blunted the length-dependent increase in Ca(2+)-sensitivity induced upon PKA-mediated phosphorylation. Since the drop in Ca(2+)-sensitivity at physiological Ca(2+)-concentrations is relatively large phosphorylation of Ser42/44 may result in a decrease of force and associated ATP utilization in the human heart.
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