Back to the future: new techniques show that forgotten phosphorylation sites are present in contractile proteins of the heart whilst intensively studied sites appear to be absent
Open accessAbstract
It is well established that several key proteins of the contractile apparatus are phosphoproteins.This includes myosin binding protein C (MyBP-C), troponin T and troponin I.It is also generally accepted that phosphorylation of these proteins alters their functional properties and that this modulation of function through the action of kinases and phosphatases plays a role in tuning the contractile apparatus to physiological demands.The prime example of this is phosphorylation of troponin I and MyBP-C by PKA as part of inotropic and lusitropic responses to b-adrenergic stimulation.What is considerably less certain is the 'where' and 'when' of these phosphorylations.The sites of contractile protein phosphorylation by kinases such as PKA and PKC have been determined in vitro and the consequences of changes in phosphorylation at these sites have been investigated by site directed mutagenesis and transgenic mouse models.What has not been determined is whether these predominantly in vitro measurements in purified proteins and in rodent models have any relevance to the human heart in vivo.Recently several papers have addressed this question with new techniques and the results have been surprising and somewhat disconcerting.Phosphorylation in human and rat troponin I and troponin T has recently been studied using electrospray ionisation and Fourier transform mass spectrometry (Zabrouskov et al. 2008;Sancho Solis et al.
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PTMs of sarcomeric proteins are important mediators of cardiac signaling and exert various effects on contractile function.
“The PTMs of sarcomeric proteins are known to be important mediators of cardiac signaling and exert various effects on contractile function (13–17).”
From Distinct hypertrophic cardiomyopathy genotypes result in convergent sarcomeric proteoform profiles revealed by top-down proteomics (2020) · cites this paper as [16]
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Bowling, N. L., Walsh, R. A., Song, G., Estridge, T. B., Sandusky, G. E., Fouts, R. L., Mintze, K., Pickard, T., Roden, R. L., Bristow, M. R., et al. (1999) · Circulation · doi:10.1161/01.cir.99.3.384 · Cited by 458 · see citing works
Gautel, M., Zuffardi, O., Freiburg, A., & Labeit, S. (1995) · The EMBO Journal · doi:10.1002/j.1460-2075.1995.tb07187.x · Cited by 411 · see citing works
Regulation of cardiac contractile function by troponin I phosphorylation
LAYLAND, J., SOLARO, R., & SHAH, A. (2005) · Cardiovascular Research · doi:10.1016/j.cardiores.2004.12.022 · Cited by 385 · see citing works
van der Velden, J., Papp, Z., Zaremba, R., Boontje, N. M., DEJONG, J., Owen, V. J., Burton, P., Goldmann, P., Jaquet, K., & Stienen, G. J. M. (2002) · Cardiovascular Research · doi:10.1016/s0008-6363(02)00606-5 · Cited by 301 · see citing works
Increased Expression of Cardiac Phosphatases in Patients with End-stage Heart Failure
Neumann, J., Thomas Eschenhagen, A., Jones, L. R., Linck, B., Schmitz, W. L., Scholz, H., & Zimmermann, N. (1997) · Journal of Molecular and Cellular Cardiology · doi:10.1006/jmcc.1996.0271 · Cited by 263 · see citing works
Sumandea, M. P., Pyle, W. G., Kobayashi, T., de Tombe, P. P., & Solaro, R. J. (2003) · Journal of Biological Chemistry · doi:10.1074/jbc.m306325200 · Cited by 182 · see citing works
Messer, A. E., Jacques, A. M., & Marston, S. B. (2006) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2006.08.017 · Cited by 174 · see citing works
Self-citationNoland, T. A., Raynor, R. L., & Kuo, J. F. (1989) · Journal of Biological Chemistry · doi:10.1016/s0021-9258(19)47130-5 · Cited by 131 · see citing works
Zabrouskov, V., Ge, Y., Schwartz, J. C., & Walker, J. W. (2008) · Molecular & Cellular Proteomics · doi:10.1074/mcp.m700524-mcp200 · Cited by 117 · see citing works
Self-citationMyosin binding protein C phosphorylation in normal, hypertrophic and failing human heart muscle
Jacques, A. M., Copeland, O., Messer, A. E., Gallon, C. E., King, K., McKenna, W. J., Tsang, V. T., & Marston, S. B. (2008) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2008.05.020 · Cited by 109 · see citing works
Self-citationBuscemi, N., Foster, D. B., Neverova, I., & Eyk, J. E. V. (2002) · Circulation Research · doi:10.1161/01.res.0000035246.27856.53 · Cited by 92 · see citing works
Yuan, C., Guo, Y., Ravi, R., Przyklenk, K., Shilkofski, N. A., Diez, R., Cole, R. N., & Murphy, A. M. (2006) · PROTEOMICS · doi:10.1002/pmic.200500894 · Cited by 88 · see citing works
Troponin phosphorylation and myofilament Ca2+-sensitivity in heart failure: Increased or decreased?
Marston, S. B., & de Tombe, P. P. (2008) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2008.07.004 · Cited by 77 · see citing works
Self-citationSites phosphorylated in bovine cardiac troponin T and I
Swiderek, K. M., Jaquet, K., Meyer, H. E., et al. (1990) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1990.tb15612.x · Cited by 63 · see citing works
Solis, R. S., Ge, Y., & Walker, J. W. (2008) · Journal of Muscle Research and Cell Motility · doi:10.1007/s10974-009-9168-y · Cited by 50 · see citing works
Self-citationSome properties of cardiac troponin T structure
Gusev, N. B., Barskaya, N. V., Verin, A. D., et al. (1983) · Biochemical Journal · doi:10.1042/bj2130123 · Cited by 49 · see citing works
Isolation and some properties of troponin T kinase from rabbit skeletal muscle
Gusev, N. B., Dobrovol'skiĭ, A. B., & Severin, S. E. (1980) · Biochemical Journal · doi:10.1042/bj1890219 · Cited by 41 · see citing works
Prevention of Myofilament Dysfunction by β-Blocker Therapy in Postinfarct Remodeling
Duncker, D. J., Boontje, N. M., Merkus, D., Versteilen, A. M. G., Krysiak, J., Mearini, G., El‐Armouche, A., de Beer, V. J., Lamers, J. M. J., Carrier, L., et al. (2009) · Circulation Heart Failure · doi:10.1161/circheartfailure.108.806125 · Cited by 40 · see citing works
Isolation and characterization of a highly phosphorylated troponin from bovine heart
Beier, N., Jaquet, K., Schnackerz, K. D., et al. (1988) · European Journal of Biochemistry · doi:10.1111/j.1432-1033.1988.tb14285.x · Cited by 26 · see citing works
Jaquet, K., Korte, K., Schnackerz, K. D., et al. (1993) · Biochemistry · doi:10.1021/bi00213a016 · Cited by 25 · see citing works
Messer, A. E., Gallon, C. E., & Marston, S. B. (2009) · Biophysical Journal · doi:10.1016/j.bpj.2008.12.2586 · Cited by 2 · see citing works
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Tucholski, T., Cai, W., Gregorich, Z. R., Bayne, E. F., Mitchell, S. D., McIlwain, S. J., de Lange, W. J., Wrobbel, M., Karp, H., Hite, Z., et al. (2020) · Proceedings of the National Academy of Sciences · doi:10.1073/pnas.2006764117 · Cited by 107 · see citing works
Self-citationAugmented Phosphorylation of Cardiac Troponin I in Hypertensive Heart Failure
Dong, X., Sumandea, C. A., Chen, Y.-C., Garcia-Cazarin, M. L., Zhang, J., Balke, C. W., Sumandea, M. P., & Ge, Y. (2012) · Journal of Biological Chemistry · doi:10.1074/jbc.m111.293258 · Cited by 99 · see citing works
Kooij, V., Saes, M., Jaquet, K., Zaremba, R., Foster, D. B., Murphy, A. M., dos Remedios, C., van der Velden, J., & Stienen, G. J. M. (2010) · Journal of Molecular and Cellular Cardiology · doi:10.1016/j.yjmcc.2010.01.002 · Cited by 73 · see citing works
- Authors
- Marston, S. B., & Walker, J. W.
- Affiliations
- Imperial College London (GB)
- University of Arizona (US)
- Corresponding author
- Marston, Steven B.
- ORCID
- Marston, Steven B.
- Venue
- Journal of Muscle Research and Cell Motility
- Published
- 2009-06
- Volume
- 30
- Issue
- 3-4
- Pages
- 93-95
- ISSN
- 0142-4319 (ISSN-L)
- 1573-2657
- PMC
- PMC2734264
- OpenAlex
- W2019345701
- Cited by
- 16
- References
- 21
- Citations by year
- 2023: 2 · 2020: 1 · 2016: 1 · 2015: 1 · 2014: 1 · 2013: 1 · 2012: 1
- FWCI
- 1.94
- Type
- journal article
- Language
- en
- Open access
- hybrid
- doi.org
- Licence
- cc-by-nc
- Locations
- Journal of Muscle Research and Cell Motility (publishedVersion, cc-by-nc)
- PubMed Central (publishedVersion)
- PubMed (publishedVersion)
- Spiral (Imperial College London) (submittedVersion, other-oa)
- Topics
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiomyopathy and Myosin Studies
- Physical Sciences › Chemistry › Spectroscopy › Advanced Proteomics Techniques and Applications
- Health Sciences › Medicine › Cardiology and Cardiovascular Medicine › Cardiac electrophysiology and arrhythmias
- Keywords
- protein phosphorylation, cardiac contractile proteins, myosin binding protein C, troponin I, troponin T, protein kinase A, protein kinase C, phosphorylation sites, human heart, phosphoproteomics
- MeSH terms
- Myosin Binding Protein C, Animals, Carrier Proteins, Contractile Proteins, Humans, Myocardial Contraction, Phosphorylation, Protein Kinases, Troponin I, Troponin T
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