PKC alpha-Specific Phosphorylation of the Troponin Complex in Human Myocardium: A Functional and Proteomics Analysis

V. Kooij; P.B. Zhang; S.R. Piersma; V. Sequeira Oliveira; N. Boontje; P.J.M. Wijnker; C.R. Jimenez; K.E. Jaquet; C. dos Remedios; A.M. Murphy; J.E. van Eyk; J. van der Velden; G.J.M. Stienen

doi:https://doi.org/10.1371/journal.pone.0074847

PKC alpha-Specific Phosphorylation of the Troponin Complex in Human Myocardium: A Functional and Proteomics Analysis

V. Kooij, P.B. Zhang, S.R. Piersma, V. Sequeira Oliveira, N. Boontje, P.J.M. Wijnker, C.R. Jimenez, K.E. Jaquet, C. dos Remedios, A.M. Murphy, J.E. van Eyk, J. van der Velden, G.J.M. Stienen

Research output: Contribution to journal › Article › Academic › peer-review

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Abstract

Aims:Protein kinase Cα (PKCα) is one of the predominant PKC isoforms that phosphorylate cardiac troponin. PKCα is implicated in heart failure and serves as a potential therapeutic target, however, the exact consequences for contractile function in human myocardium are unclear. This study aimed to investigate the effects of PKCα phosphorylation of cardiac troponin (cTn) on myofilament function in human failing cardiomyocytes and to resolve the potential targets involved.Methods and Results:Endogenous cTn from permeabilized cardiomyocytes from patients with end-stage idiopathic dilated cardiomyopathy was exchanged (∼69%) with PKCα-treated recombinant human cTn (cTn (DD+PKCα)). This complex has Ser23/24 on cTnI mutated into aspartic acids (D) to rule out in vitro cross-phosphorylation of the PKA sites by PKCα. Isometric force was measured at various [Ca

Original language	English
Article number	e74847
Number of pages	10
Journal	PLOS ONE
Volume	8
Issue number	10
DOIs	https://doi.org/10.1371/journal.pone.0074847
Publication status	Published - 2013

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Cite this

Kooij, V., Zhang, P. B., Piersma, S. R., Sequeira Oliveira, V., Boontje, N., Wijnker, P. J. M., Jimenez, C. R., Jaquet, K. E., dos Remedios, C., Murphy, A. M., van Eyk, J. E., van der Velden, J., & Stienen, G. J. M. (2013). PKC alpha-Specific Phosphorylation of the Troponin Complex in Human Myocardium: A Functional and Proteomics Analysis. PLOS ONE, 8(10), Article e74847. https://doi.org/10.1371/journal.pone.0074847

@article{04b732d66ab743bfa441076f6063b65c,

title = "PKC alpha-Specific Phosphorylation of the Troponin Complex in Human Myocardium: A Functional and Proteomics Analysis",

abstract = "Aims:Protein kinase Cα (PKCα) is one of the predominant PKC isoforms that phosphorylate cardiac troponin. PKCα is implicated in heart failure and serves as a potential therapeutic target, however, the exact consequences for contractile function in human myocardium are unclear. This study aimed to investigate the effects of PKCα phosphorylation of cardiac troponin (cTn) on myofilament function in human failing cardiomyocytes and to resolve the potential targets involved.Methods and Results:Endogenous cTn from permeabilized cardiomyocytes from patients with end-stage idiopathic dilated cardiomyopathy was exchanged (∼69%) with PKCα-treated recombinant human cTn (cTn (DD+PKCα)). This complex has Ser23/24 on cTnI mutated into aspartic acids (D) to rule out in vitro cross-phosphorylation of the PKA sites by PKCα. Isometric force was measured at various [Ca",

author = "V. Kooij and P.B. Zhang and S.R. Piersma and {Sequeira Oliveira}, V. and N. Boontje and P.J.M. Wijnker and C.R. Jimenez and K.E. Jaquet and {dos Remedios}, C. and A.M. Murphy and {van Eyk}, J.E. and {van der Velden}, J. and G.J.M. Stienen",

year = "2013",

doi = "https://doi.org/10.1371/journal.pone.0074847",

language = "English",

volume = "8",

journal = "PLOS ONE",

issn = "1932-6203",

publisher = "Public Library of Science",

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}

Kooij, V, Zhang, PB, Piersma, SR, Sequeira Oliveira, V, Boontje, N, Wijnker, PJM, Jimenez, CR, Jaquet, KE, dos Remedios, C, Murphy, AM, van Eyk, JE, van der Velden, J & Stienen, GJM 2013, 'PKC alpha-Specific Phosphorylation of the Troponin Complex in Human Myocardium: A Functional and Proteomics Analysis', PLOS ONE, vol. 8, no. 10, e74847. https://doi.org/10.1371/journal.pone.0074847

TY - JOUR

T1 - PKC alpha-Specific Phosphorylation of the Troponin Complex in Human Myocardium: A Functional and Proteomics Analysis

AU - Kooij, V.

AU - Zhang, P.B.

AU - Piersma, S.R.

AU - Sequeira Oliveira, V.

AU - Boontje, N.

AU - Wijnker, P.J.M.

AU - Jimenez, C.R.

AU - Jaquet, K.E.

AU - dos Remedios, C.

AU - Murphy, A.M.

AU - van Eyk, J.E.

AU - van der Velden, J.

AU - Stienen, G.J.M.

PY - 2013

Y1 - 2013

N2 - Aims:Protein kinase Cα (PKCα) is one of the predominant PKC isoforms that phosphorylate cardiac troponin. PKCα is implicated in heart failure and serves as a potential therapeutic target, however, the exact consequences for contractile function in human myocardium are unclear. This study aimed to investigate the effects of PKCα phosphorylation of cardiac troponin (cTn) on myofilament function in human failing cardiomyocytes and to resolve the potential targets involved.Methods and Results:Endogenous cTn from permeabilized cardiomyocytes from patients with end-stage idiopathic dilated cardiomyopathy was exchanged (∼69%) with PKCα-treated recombinant human cTn (cTn (DD+PKCα)). This complex has Ser23/24 on cTnI mutated into aspartic acids (D) to rule out in vitro cross-phosphorylation of the PKA sites by PKCα. Isometric force was measured at various [Ca

AB - Aims:Protein kinase Cα (PKCα) is one of the predominant PKC isoforms that phosphorylate cardiac troponin. PKCα is implicated in heart failure and serves as a potential therapeutic target, however, the exact consequences for contractile function in human myocardium are unclear. This study aimed to investigate the effects of PKCα phosphorylation of cardiac troponin (cTn) on myofilament function in human failing cardiomyocytes and to resolve the potential targets involved.Methods and Results:Endogenous cTn from permeabilized cardiomyocytes from patients with end-stage idiopathic dilated cardiomyopathy was exchanged (∼69%) with PKCα-treated recombinant human cTn (cTn (DD+PKCα)). This complex has Ser23/24 on cTnI mutated into aspartic acids (D) to rule out in vitro cross-phosphorylation of the PKA sites by PKCα. Isometric force was measured at various [Ca

U2 - https://doi.org/10.1371/journal.pone.0074847

DO - https://doi.org/10.1371/journal.pone.0074847

M3 - Article

C2 - 24116014

SN - 1932-6203

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JO - PLOS ONE

JF - PLOS ONE

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