ArticleProtein science : a publication of the Protein Society2011
A preferred AMPK phosphorylation site adjacent to the inhibitory loop of cardiac and skeletal troponin I.
Article in Protein science : a publication of the Protein Society, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 17 papers.
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Who cites it
17 citing papers in PubMed, 26 citations in OpenAlex.
- Single-molecule imaging reveals how mavacamten and PKA modulate ATP turnover in skeletal muscle myofibrils.The Journal of general physiology · 2023Article
- Liver Kinase B1 complex acts as a novel modifier of myofilament function and localizes to the Z-disk in cardiac myocytes.Archives of biochemistry and biophysics · 2016Article
- Functional phosphorylation sites in cardiac myofilament proteins are evolutionarily conserved in skeletal myofilament proteins.Physiological genomics · 2016Article
- Comprehensive Characterization of AMP-Activated Protein Kinase Catalytic Domain by Top-Down Mass Spectrometry.Journal of the American Society for Mass Spectrometry · 2016Article
- TNNI1, TNNI2 and TNNI3: Evolution, regulation, and protein structure-function relationships.Gene · 2016Review
- The Modulation of Cardiac Contractile Function by the Pharmacological and Toxicological Effects of Urocortin2.Toxicological sciences : an official journal of the Society of Toxicology · 2015Article
- LKB1/Mo25/STRAD uniquely impacts sarcomeric contractile function and posttranslational modification.Biophysical journal · 2015Article
- Top-down mass spectrometry of cardiac myofilament proteins in health and disease.Proteomics. Clinical applications · 2014Review
- The art of the deal in myofilament modulation of function.Journal of molecular and cellular cardiology · 2014Article
- Combined troponin I Ser-150 and Ser-23/24 phosphorylation sustains thin filament Ca(2+) sensitivity and accelerates deactivation in an acidic environment.Journal of molecular and cellular cardiology · 2014Article
- Alpha1 catalytic subunit of AMPK modulates contractile function of cardiomyocytes through phosphorylation of troponin I.Life sciences · 2014Article
- Gene regulation, alternative splicing, and posttranslational modification of troponin subunits in cardiac development and adaptation: a focused review.Frontiers in physiology · 2014Review
- Sexually dimorphic myofilament function and cardiac troponin I phosphospecies distribution in hypertrophic cardiomyopathy mice.Archives of biochemistry and biophysics · 2013Article
- Integration of troponin I phosphorylation with cardiac regulatory networks.Circulation research · 2013Review
- AMP-activated protein kinase phosphorylates cardiac troponin I at Ser-150 to increase myofilament calcium sensitivity and blunt PKA-dependent function.The Journal of biological chemistry · 2012Article
- Sphingomyelinase depresses force and calcium sensitivity of the contractile apparatus in mouse diaphragm muscle fibers.Journal of applied physiology (Bethesda, Md. : 1985) · 2012Article
- Ablation of p21-activated kinase-1 in mice promotes isoproterenol-induced cardiac hypertrophy in association with activation of Erk1/2 and inhibition of protein phosphatase 2A.Journal of molecular and cellular cardiology · 2011Article
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
5'-AMP-activated protein kinase (AMPK) is a serine/threonine protein kinase that is activated when cellular AMP to ATP ratios rise, potentially serving as a key regulator of cellular energetics. Among the known targets of AMPK are catabolic and anabolic enzymes, but little is known about the ability of this kinase to phosphorylate myofilament proteins and thereby regulating the contractile apparatus of striated muscles. Here, we demonstrate that troponin I isoforms of cardiac (cTnI) and fast skeletal (fsTnI) muscles are readily phosphorylated by AMPK. For cTnI, two highly conserved serine residues were identified as AMPK sites using a combination of high-resolution top-down electron capture dissociation mass spectrometry, (32) P-incorporation, synthetic peptides, phospho-specific antibodies, and site-directed mutagenesis. These AMPK sites in cTnI were Ser149 adjacent to the inhibitory loop and Ser22 in the cardiac-specific N-terminal extension, at the level of cTnI peptides, the intact cTnI subunit, whole cardiac troponin complexes and skinned cardiomyocytes. Phosphorylation time-course experiments revealed that Ser149 was the preferred site, because it was phosphorylated 12-16-fold faster than Ser22 in cTnI. Ser117 in fsTnI, analogous to Ser149 in cTnI, was phosphorylated with similar kinetics as cTnI Ser149. Hence, the master energy-sensing protein AMPK emerges as a possibly important regulator of cardiac and skeletal contractility via phosphorylation of a preferred site adjacent to the inhibitory loop of the thin filament protein TnI.
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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.