ArticleJournal of molecular and cellular cardiology2014
Cardiac troponin I tyrosine 26 phosphorylation decreases myofilament Ca2+ sensitivity and accelerates deactivation.
Article in Journal of molecular and cellular cardiology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 28 papers.
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Who cites it
28 citing papers in PubMed, 34 citations in OpenAlex.
- Chamber-specific regulation of myofilament Ca2+ sensitivity by nNOSβ via troponin I phosphorylation: Predominance in the right ventricle.The Journal of general physiology · 2026Article
- The Orally Available Ghrelin Receptor-Agonist AC01 Improves Systolic Function in HFrEF Mice and Nonhuman Primates.JACC. Basic to translational science · 2026Article
- Troponin I - a comprehensive review of its function, structure, evolution, and role in muscle diseases.Animal cells and systems · 2025Review
- Abnormal phosphorylation / dephosphorylation and CaHeart failure reviews · 2024Review
- Troponin I Tyrosine Phosphorylation Beneficially Accelerates Diastolic Function.Circulation research · 2024Article
- Thin filament regulation of cardiac muscle power output: Implications for targets to improve human failing hearts.The Journal of general physiology · 2023Article
- The lack of Troponin I Ser-23/24 phosphorylation is detrimental to in vivo cardiac function and exacerbates cardiac disease.Journal of molecular and cellular cardiology · 2023Article
- Molecular regulation of stretch activation.American journal of physiology. Cell physiology · 2022Article
- Alteration in tyrosine phosphorylation of cardiac proteome and EGFR pathway contribute to hypertrophic cardiomyopathy.Communications biology · 2022Article
- Truncation of the N-terminus of cardiac troponin I initiates adaptive remodeling of the myocardial proteosome via phosphorylation of mechano-sensitive signaling pathways.Molecular and cellular biochemistry · 2022Article
- Protein tyrosine phosphatase receptor-ζ1 deletion triggers defective heart morphogenesis in mice and zebrafish.American journal of physiology. Heart and circulatory physiology · 2022Article
- Quantitative Analysis of the Cardiac Phosphoproteome in Response to Acute β-Adrenergic Receptor Stimulation In Vivo.International journal of molecular sciences · 2021Article
- NHJournal of cellular signaling · 2021Article
- Heart Failure in Humans Reduces Contractile Force in Myocardium From Both Ventricles.JACC. Basic to translational science · 2020Article
- Site-specific acetyl-mimetic modification of cardiac troponin I modulates myofilament relaxation and calcium sensitivity.Journal of molecular and cellular cardiology · 2020Article
- Characterizing the influence of chronic hypobaric hypoxia on diaphragmatic myofilament contractile function and phosphorylation in high-altitude deer mice and low-altitude white-footed mice.Journal of comparative physiology. B, Biochemical, systemic, and environmental physiology · 2019Article
- Troponin I modulation of cardiac performance: Plasticity in the survival switch.Archives of biochemistry and biophysics · 2019Review
- Chronic Calmodulin-Kinase II Activation Drives Disease Progression in Mutation-Specific Hypertrophic Cardiomyopathy.Circulation · 2019Article
- Biophysical Derangements in Genetic Cardiomyopathies.Heart failure clinics · 2018Review
- Long-Term Biased β-Arrestin Signaling Improves Cardiac Structure and Function in Dilated Cardiomyopathy.Circulation · 2017Article
Corrections and comments
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Authors and funding
8 authors at 3 institutions in 1 country.
Funding
Abstract
Troponin I (TnI), the inhibitory subunit of the troponin complex, can be phosphorylated as a key regulatory mechanism to alter the calcium regulation of contraction. Recent work has identified phosphorylation of TnI Tyr-26 in the human heart with unknown functional effects. We hypothesized that TnI Tyr-26N-terminal phosphorylation decreases calcium sensitivity of the thin filament, similar to the desensitizing effects of TnI Ser-23/24 phosphorylation. Our results demonstrate that Tyr-26 phosphorylation and pseudo-phosphorylation decrease calcium binding to troponin C (TnC) on the thin filament and calcium sensitivity of force development to a similar magnitude as TnI Ser-23/24 pseudo-phosphorylation. To investigate the effects of TnI Tyr-26 phosphorylation on myofilament deactivation, we measured the rate of calcium dissociation from TnC. Results demonstrate that filaments containing Tyr-26 pseudo-phosphorylated TnI accelerate the rate of calcium dissociation from TnC similar to that of TnI Ser-23/24. Finally, to assess functional integration of TnI Tyr-26 with Ser-23/24 phosphorylation, we generated recombinant TnI phospho-mimetic substitutions at all three residues. Our biochemical analyses demonstrated no additive effect on calcium sensitivity or calcium-sensitive force development imposed by Tyr-26 and Ser-23/24 phosphorylation integration. However, integration of Tyr-26 phosphorylation with pseudo-phosphorylated Ser-23/24 further accelerated thin filament deactivation. Our findings suggest that TnI Tyr-26 phosphorylation functions similarly to Ser-23/24N-terminal phosphorylation to decrease myofilament calcium sensitivity and accelerate myofilament relaxation. Furthermore, Tyr-26 phosphorylation can buffer the desensitization of Ser-23/24 phosphorylation while further accelerating thin filament deactivation. Therefore, the functional integration of TnI phosphorylation may be a common mechanism to modulate Ser-23/24 phosphorylation function.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.