In Vivo Phosphoproteomics Analysis Reveals the Cardiac Targets of β-Adrenergic Receptor Signaling

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In Vivo Phosphoproteomics Analysis Reveals the Cardiac Targets of β-Adrenergic Receptor Signaling. / Lundby, Alicia; Andersen, Martin N; Steffensen, Annette B; Horn, Heiko; Kelstrup, Christian D; Francavilla, Chiara; Jensen, Lars J; Schmitt, Nicole; Thomsen, Morten B; Olsen, Jesper V.

I: Science Signaling, Bind 6, Nr. 278, 04.06.2013, s. rs11.

Publikation: Bidrag til tidsskriftTidsskriftartikelForskningfagfællebedømt

Harvard

Lundby, A, Andersen, MN, Steffensen, AB, Horn, H, Kelstrup, CD, Francavilla, C, Jensen, LJ, Schmitt, N, Thomsen, MB & Olsen, JV 2013, 'In Vivo Phosphoproteomics Analysis Reveals the Cardiac Targets of β-Adrenergic Receptor Signaling', Science Signaling, bind 6, nr. 278, s. rs11. https://doi.org/10.1126/scisignal.2003506

APA

Lundby, A., Andersen, M. N., Steffensen, A. B., Horn, H., Kelstrup, C. D., Francavilla, C., ... Olsen, J. V. (2013). In Vivo Phosphoproteomics Analysis Reveals the Cardiac Targets of β-Adrenergic Receptor Signaling. Science Signaling, 6(278), rs11. https://doi.org/10.1126/scisignal.2003506

Vancouver

Lundby A, Andersen MN, Steffensen AB, Horn H, Kelstrup CD, Francavilla C o.a. In Vivo Phosphoproteomics Analysis Reveals the Cardiac Targets of β-Adrenergic Receptor Signaling. Science Signaling. 2013 jun 4;6(278):rs11. https://doi.org/10.1126/scisignal.2003506

Author

Lundby, Alicia ; Andersen, Martin N ; Steffensen, Annette B ; Horn, Heiko ; Kelstrup, Christian D ; Francavilla, Chiara ; Jensen, Lars J ; Schmitt, Nicole ; Thomsen, Morten B ; Olsen, Jesper V. / In Vivo Phosphoproteomics Analysis Reveals the Cardiac Targets of β-Adrenergic Receptor Signaling. I: Science Signaling. 2013 ; Bind 6, Nr. 278. s. rs11.

Bibtex

@article{a5fa0aabb9cf48a6961dbe38293f57c1,
title = "In Vivo Phosphoproteomics Analysis Reveals the Cardiac Targets of β-Adrenergic Receptor Signaling",
abstract = "β-Blockers are widely used to prevent cardiac arrhythmias and to treat hypertension by inhibiting β-adrenergic receptors (βARs) and thus decreasing contractility and heart rate. βARs initiate phosphorylation-dependent signaling cascades, but only a small number of the target proteins are known. We used quantitative in vivo phosphoproteomics to identify 670 site-specific phosphorylation changes in murine hearts in response to acute treatment with specific βAR agonists. The residues adjacent to the regulated phosphorylation sites exhibited a sequence-specific preference (R-X-X-pS/T), and integrative analysis of sequence motifs and interaction networks suggested that the kinases AMPK (adenosine 5'-monophosphate-activated protein kinase), Akt, and mTOR (mammalian target of rapamycin) mediate βAR signaling, in addition to the well-established pathways mediated by PKA (cyclic adenosine monophosphate-dependent protein kinase) and CaMKII (calcium/calmodulin-dependent protein kinase type II). We found specific regulation of phosphorylation sites on six ion channels and transporters that mediate increased ion fluxes at higher heart rates, and we showed that phosphorylation of one of these, Ser(92) of the potassium channel KV7.1, increased current amplitude. Our data set represents a quantitative analysis of phosphorylated proteins regulated in vivo upon stimulation of seven-transmembrane receptors, and our findings reveal previously unknown phosphorylation sites that regulate myocardial contractility, suggesting new potential targets for the treatment of heart disease and hypertension.",
author = "Alicia Lundby and Andersen, {Martin N} and Steffensen, {Annette B} and Heiko Horn and Kelstrup, {Christian D} and Chiara Francavilla and Jensen, {Lars J} and Nicole Schmitt and Thomsen, {Morten B} and Olsen, {Jesper V}",
year = "2013",
month = "6",
day = "4",
doi = "10.1126/scisignal.2003506",
language = "English",
volume = "6",
pages = "rs11",
journal = "Science Signaling",
issn = "1945-0877",
publisher = "American Association for the Advancement of Science",
number = "278",

}

RIS

TY - JOUR

T1 - In Vivo Phosphoproteomics Analysis Reveals the Cardiac Targets of β-Adrenergic Receptor Signaling

AU - Lundby, Alicia

AU - Andersen, Martin N

AU - Steffensen, Annette B

AU - Horn, Heiko

AU - Kelstrup, Christian D

AU - Francavilla, Chiara

AU - Jensen, Lars J

AU - Schmitt, Nicole

AU - Thomsen, Morten B

AU - Olsen, Jesper V

PY - 2013/6/4

Y1 - 2013/6/4

N2 - β-Blockers are widely used to prevent cardiac arrhythmias and to treat hypertension by inhibiting β-adrenergic receptors (βARs) and thus decreasing contractility and heart rate. βARs initiate phosphorylation-dependent signaling cascades, but only a small number of the target proteins are known. We used quantitative in vivo phosphoproteomics to identify 670 site-specific phosphorylation changes in murine hearts in response to acute treatment with specific βAR agonists. The residues adjacent to the regulated phosphorylation sites exhibited a sequence-specific preference (R-X-X-pS/T), and integrative analysis of sequence motifs and interaction networks suggested that the kinases AMPK (adenosine 5'-monophosphate-activated protein kinase), Akt, and mTOR (mammalian target of rapamycin) mediate βAR signaling, in addition to the well-established pathways mediated by PKA (cyclic adenosine monophosphate-dependent protein kinase) and CaMKII (calcium/calmodulin-dependent protein kinase type II). We found specific regulation of phosphorylation sites on six ion channels and transporters that mediate increased ion fluxes at higher heart rates, and we showed that phosphorylation of one of these, Ser(92) of the potassium channel KV7.1, increased current amplitude. Our data set represents a quantitative analysis of phosphorylated proteins regulated in vivo upon stimulation of seven-transmembrane receptors, and our findings reveal previously unknown phosphorylation sites that regulate myocardial contractility, suggesting new potential targets for the treatment of heart disease and hypertension.

AB - β-Blockers are widely used to prevent cardiac arrhythmias and to treat hypertension by inhibiting β-adrenergic receptors (βARs) and thus decreasing contractility and heart rate. βARs initiate phosphorylation-dependent signaling cascades, but only a small number of the target proteins are known. We used quantitative in vivo phosphoproteomics to identify 670 site-specific phosphorylation changes in murine hearts in response to acute treatment with specific βAR agonists. The residues adjacent to the regulated phosphorylation sites exhibited a sequence-specific preference (R-X-X-pS/T), and integrative analysis of sequence motifs and interaction networks suggested that the kinases AMPK (adenosine 5'-monophosphate-activated protein kinase), Akt, and mTOR (mammalian target of rapamycin) mediate βAR signaling, in addition to the well-established pathways mediated by PKA (cyclic adenosine monophosphate-dependent protein kinase) and CaMKII (calcium/calmodulin-dependent protein kinase type II). We found specific regulation of phosphorylation sites on six ion channels and transporters that mediate increased ion fluxes at higher heart rates, and we showed that phosphorylation of one of these, Ser(92) of the potassium channel KV7.1, increased current amplitude. Our data set represents a quantitative analysis of phosphorylated proteins regulated in vivo upon stimulation of seven-transmembrane receptors, and our findings reveal previously unknown phosphorylation sites that regulate myocardial contractility, suggesting new potential targets for the treatment of heart disease and hypertension.

U2 - 10.1126/scisignal.2003506

DO - 10.1126/scisignal.2003506

M3 - Journal article

VL - 6

SP - rs11

JO - Science Signaling

JF - Science Signaling

SN - 1945-0877

IS - 278

ER -

ID: 46129203