A novel phosphorylation site, Serine 199, in the C-terminus of cardiac troponin I regulates calcium sensitivity and susceptibility to calpain-induced proteolysis

P.J.M. Wijnker; Y. Li; P. Zhang; D.B. Foster; C. dos Remedios; J.E. van Eyk; G.J.M. Stienen; A.M. Murphy; J. van der Velden

doi:10.1016/j.yjmcc.2015.03.006

A novel phosphorylation site, Serine 199, in the C-terminus of cardiac troponin I regulates calcium sensitivity and susceptibility to calpain-induced proteolysis

P.J.M. Wijnker, Y. Li, P. Zhang, D.B. Foster, C. dos Remedios, J.E. van Eyk, G.J.M. Stienen, A.M. Murphy, J. van der Velden

Physics of Living Systems

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

Abstract

Phosphorylation of cardiac troponin I (cTnI) by protein kinase C (PKC) is implicated in cardiac dysfunction. Recently, Serine 199 (Ser199) was identified as a target for PKC phosphorylation and increased Ser199 phosphorylation occurs in end-stage failing compared with non-failing human myocardium. The functional consequences of cTnI-Ser199 phosphorylation in the heart are unknown. Therefore, we investigated the impact of phosphorylation of cTnI-Ser199 on myofilament function in human cardiac tissue and the susceptibility of cTnI to proteolysis. cTnI-Ser199 was replaced by aspartic acid (199D) or alanine (199A) to mimic phosphorylation and dephosphorylation, respectively, with recombinant wild-type (Wt) cTn as a negative control. Force development was measured at various [Ca

Original language	English
Pages (from-to)	93-103
Journal	Journal of Molecular and Cellular Cardiology
Volume	82
DOIs	https://doi.org/10.1016/j.yjmcc.2015.03.006
Publication status	Published - 2015

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Wijnker, P. J. M., Li, Y., Zhang, P., Foster, D. B., dos Remedios, C., van Eyk, J. E., Stienen, G. J. M., Murphy, A. M., & van der Velden, J. (2015). 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, 82, 93-103. https://doi.org/10.1016/j.yjmcc.2015.03.006

@article{d630e85709864fcc886acd7831d26154,

title = "A novel phosphorylation site, Serine 199, in the C-terminus of cardiac troponin I regulates calcium sensitivity and susceptibility to calpain-induced proteolysis",

abstract = "Phosphorylation of cardiac troponin I (cTnI) by protein kinase C (PKC) is implicated in cardiac dysfunction. Recently, Serine 199 (Ser199) was identified as a target for PKC phosphorylation and increased Ser199 phosphorylation occurs in end-stage failing compared with non-failing human myocardium. The functional consequences of cTnI-Ser199 phosphorylation in the heart are unknown. Therefore, we investigated the impact of phosphorylation of cTnI-Ser199 on myofilament function in human cardiac tissue and the susceptibility of cTnI to proteolysis. cTnI-Ser199 was replaced by aspartic acid (199D) or alanine (199A) to mimic phosphorylation and dephosphorylation, respectively, with recombinant wild-type (Wt) cTn as a negative control. Force development was measured at various [Ca",

author = "P.J.M. Wijnker and Y. Li and P. Zhang and D.B. Foster and {dos Remedios}, C. and {van Eyk}, J.E. and G.J.M. Stienen and A.M. Murphy and {van der Velden}, J.",

year = "2015",

doi = "10.1016/j.yjmcc.2015.03.006",

language = "English",

volume = "82",

pages = "93--103",

journal = "Journal of Molecular and Cellular Cardiology",

issn = "0022-2828",

publisher = "Academic Press Inc.",

}

Wijnker, PJM, Li, Y, Zhang, P, Foster, DB, dos Remedios, C, van Eyk, JE, Stienen, GJM, Murphy, AM & van der Velden, J 2015, '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, vol. 82, pp. 93-103. https://doi.org/10.1016/j.yjmcc.2015.03.006

TY - JOUR

T1 - A novel phosphorylation site, Serine 199, in the C-terminus of cardiac troponin I regulates calcium sensitivity and susceptibility to calpain-induced proteolysis

AU - Wijnker, P.J.M.

AU - Li, Y.

AU - Zhang, P.

AU - Foster, D.B.

AU - dos Remedios, C.

AU - van Eyk, J.E.

AU - Stienen, G.J.M.

AU - Murphy, A.M.

AU - van der Velden, J.

PY - 2015

Y1 - 2015

N2 - Phosphorylation of cardiac troponin I (cTnI) by protein kinase C (PKC) is implicated in cardiac dysfunction. Recently, Serine 199 (Ser199) was identified as a target for PKC phosphorylation and increased Ser199 phosphorylation occurs in end-stage failing compared with non-failing human myocardium. The functional consequences of cTnI-Ser199 phosphorylation in the heart are unknown. Therefore, we investigated the impact of phosphorylation of cTnI-Ser199 on myofilament function in human cardiac tissue and the susceptibility of cTnI to proteolysis. cTnI-Ser199 was replaced by aspartic acid (199D) or alanine (199A) to mimic phosphorylation and dephosphorylation, respectively, with recombinant wild-type (Wt) cTn as a negative control. Force development was measured at various [Ca

AB - Phosphorylation of cardiac troponin I (cTnI) by protein kinase C (PKC) is implicated in cardiac dysfunction. Recently, Serine 199 (Ser199) was identified as a target for PKC phosphorylation and increased Ser199 phosphorylation occurs in end-stage failing compared with non-failing human myocardium. The functional consequences of cTnI-Ser199 phosphorylation in the heart are unknown. Therefore, we investigated the impact of phosphorylation of cTnI-Ser199 on myofilament function in human cardiac tissue and the susceptibility of cTnI to proteolysis. cTnI-Ser199 was replaced by aspartic acid (199D) or alanine (199A) to mimic phosphorylation and dephosphorylation, respectively, with recombinant wild-type (Wt) cTn as a negative control. Force development was measured at various [Ca

U2 - 10.1016/j.yjmcc.2015.03.006

DO - 10.1016/j.yjmcc.2015.03.006

M3 - Article

SN - 0022-2828

VL - 82

SP - 93

EP - 103

JO - Journal of Molecular and Cellular Cardiology

JF - Journal of Molecular and Cellular Cardiology

ER -

A novel phosphorylation site, Serine 199, in the C-terminus of cardiac troponin I regulates calcium sensitivity and susceptibility to calpain-induced proteolysis

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