The relative relevance of phosphorylation of the Thr¹⁷ residue of phospholamban is different at different levels of β-adrenergic stimulation
- Autores
- Said, María Matilde; Mundiña-Weilenmann, Cecilia; Vittone, Leticia Beatriz; Mattiazzi, Alicia Ramona
- Año de publicación
- 2002
- Idioma
- español castellano
- Tipo de recurso
- artículo
- Estado
- versión publicada
- Descripción
- Contractility and relaxation measurements were combined with the determination of total phospholamban (PLB) phosphorylation and the immunodetection of PLB-phosphorylation sites in the intact, beating rat heart to identify the contributions of PLB phosphorylation at the Thr¹⁷ and Ser¹⁶ residues at different levels of β-adrenoceptor stimulation. Whereas with 30-300 nM isoproterenol, phosphorylation of Thr¹⁷, the Ca²⁺-calmodulin-dependent protein kinase-II (CaMKII) site and Ser¹⁶, the protein kinase A (PKA) site, contributed approximately 50% each to PLB phosphorylation, and both participated in the relaxant action of isoproterenol, at lower a level of β-adrenoceptor stimulation (isoproterenol 0.3-3 nM), both effects were exclusively due to Ser¹⁶ phosphorylation. Increasing [Ca]o at 3 nM isoproterenol, to obtain an increase in contractility comparable to that produced by 30 nM isoproterenol, significantly increased Thr¹⁷ phosphorylation and the relaxant effect produced by 3 nM isoproterenol. An increase in Thr¹⁷ phosphorylation and in the relaxant effect of 3 nM isoproterenol was also obtained by phosphatase inhibition (okadaic acid). In this case, Ser¹⁶ phosphorylation was also increased. Moreover, perfusion with 30 nM isoproterenol in the presence of the PKA inhibitor H-89 decreased phosphorylation at both PLB residues and diminished the inotropic and relaxant responses to the β-agonist. The relative contribution of Thr¹⁷ phosphorylation to the isoproterenol-induced phosphorylation of PLB and relaxation thus increased with the level of β-adrenoceptor stimulation and the consequent increase in PKA activity. The lack of Thr¹⁷ phosphorylation at low isoproterenol concentrations might therefore be attributed to a level of PKA activity insufficient to increase [Ca]i to activate the CaMKII system and/or to inhibit the phosphatase that dephosphorylates PLB.
Centro de Investigaciones Cardiovasculares - Materia
-
Medicina
Phospholamban phosphorylation sites
β-Adrenoceptor stimulation
Myocardial relaxation - Nivel de accesibilidad
- acceso abierto
- Condiciones de uso
- http://creativecommons.org/licenses/by/4.0/
- Repositorio
- Institución
- Universidad Nacional de La Plata
- OAI Identificador
- oai:sedici.unlp.edu.ar:10915/144219
Ver los metadatos del registro completo
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The relative relevance of phosphorylation of the Thr¹⁷ residue of phospholamban is different at different levels of β-adrenergic stimulationSaid, María MatildeMundiña-Weilenmann, CeciliaVittone, Leticia BeatrizMattiazzi, Alicia RamonaMedicinaPhospholamban phosphorylation sitesβ-Adrenoceptor stimulationMyocardial relaxationContractility and relaxation measurements were combined with the determination of total phospholamban (PLB) phosphorylation and the immunodetection of PLB-phosphorylation sites in the intact, beating rat heart to identify the contributions of PLB phosphorylation at the Thr¹⁷ and Ser¹⁶ residues at different levels of β-adrenoceptor stimulation. Whereas with 30-300 nM isoproterenol, phosphorylation of Thr¹⁷, the Ca²⁺-calmodulin-dependent protein kinase-II (CaMKII) site and Ser¹⁶, the protein kinase A (PKA) site, contributed approximately 50% each to PLB phosphorylation, and both participated in the relaxant action of isoproterenol, at lower a level of β-adrenoceptor stimulation (isoproterenol 0.3-3 nM), both effects were exclusively due to Ser¹⁶ phosphorylation. Increasing [Ca]<sub>o</sub> at 3 nM isoproterenol, to obtain an increase in contractility comparable to that produced by 30 nM isoproterenol, significantly increased Thr¹⁷ phosphorylation and the relaxant effect produced by 3 nM isoproterenol. An increase in Thr¹⁷ phosphorylation and in the relaxant effect of 3 nM isoproterenol was also obtained by phosphatase inhibition (okadaic acid). In this case, Ser¹⁶ phosphorylation was also increased. Moreover, perfusion with 30 nM isoproterenol in the presence of the PKA inhibitor H-89 decreased phosphorylation at both PLB residues and diminished the inotropic and relaxant responses to the β-agonist. The relative contribution of Thr¹⁷ phosphorylation to the isoproterenol-induced phosphorylation of PLB and relaxation thus increased with the level of β-adrenoceptor stimulation and the consequent increase in PKA activity. The lack of Thr¹⁷ phosphorylation at low isoproterenol concentrations might therefore be attributed to a level of PKA activity insufficient to increase [Ca]<sub>i</sub> to activate the CaMKII system and/or to inhibit the phosphatase that dephosphorylates PLB.Centro de Investigaciones Cardiovasculares2002-08info:eu-repo/semantics/articleinfo:eu-repo/semantics/publishedVersionArticulohttp://purl.org/coar/resource_type/c_6501info:ar-repo/semantics/articuloapplication/pdf801-809http://sedici.unlp.edu.ar/handle/10915/144219spainfo:eu-repo/semantics/altIdentifier/issn/0031-6768info:eu-repo/semantics/altIdentifier/issn/1432-2013info:eu-repo/semantics/altIdentifier/doi/10.1007/s00424-002-0885-yinfo:eu-repo/semantics/altIdentifier/pmid/12355181info:eu-repo/semantics/openAccesshttp://creativecommons.org/licenses/by/4.0/Creative Commons Attribution 4.0 International (CC BY 4.0)reponame:SEDICI (UNLP)instname:Universidad Nacional de La Platainstacron:UNLP2025-09-29T11:32:26Zoai:sedici.unlp.edu.ar:10915/144219Institucionalhttp://sedici.unlp.edu.ar/Universidad públicaNo correspondehttp://sedici.unlp.edu.ar/oai/snrdalira@sedici.unlp.edu.arArgentinaNo correspondeNo correspondeNo correspondeopendoar:13292025-09-29 11:32:27.101SEDICI (UNLP) - Universidad Nacional de La Platafalse |
dc.title.none.fl_str_mv |
The relative relevance of phosphorylation of the Thr¹⁷ residue of phospholamban is different at different levels of β-adrenergic stimulation |
title |
The relative relevance of phosphorylation of the Thr¹⁷ residue of phospholamban is different at different levels of β-adrenergic stimulation |
spellingShingle |
The relative relevance of phosphorylation of the Thr¹⁷ residue of phospholamban is different at different levels of β-adrenergic stimulation Said, María Matilde Medicina Phospholamban phosphorylation sites β-Adrenoceptor stimulation Myocardial relaxation |
title_short |
The relative relevance of phosphorylation of the Thr¹⁷ residue of phospholamban is different at different levels of β-adrenergic stimulation |
title_full |
The relative relevance of phosphorylation of the Thr¹⁷ residue of phospholamban is different at different levels of β-adrenergic stimulation |
title_fullStr |
The relative relevance of phosphorylation of the Thr¹⁷ residue of phospholamban is different at different levels of β-adrenergic stimulation |
title_full_unstemmed |
The relative relevance of phosphorylation of the Thr¹⁷ residue of phospholamban is different at different levels of β-adrenergic stimulation |
title_sort |
The relative relevance of phosphorylation of the Thr¹⁷ residue of phospholamban is different at different levels of β-adrenergic stimulation |
dc.creator.none.fl_str_mv |
Said, María Matilde Mundiña-Weilenmann, Cecilia Vittone, Leticia Beatriz Mattiazzi, Alicia Ramona |
author |
Said, María Matilde |
author_facet |
Said, María Matilde Mundiña-Weilenmann, Cecilia Vittone, Leticia Beatriz Mattiazzi, Alicia Ramona |
author_role |
author |
author2 |
Mundiña-Weilenmann, Cecilia Vittone, Leticia Beatriz Mattiazzi, Alicia Ramona |
author2_role |
author author author |
dc.subject.none.fl_str_mv |
Medicina Phospholamban phosphorylation sites β-Adrenoceptor stimulation Myocardial relaxation |
topic |
Medicina Phospholamban phosphorylation sites β-Adrenoceptor stimulation Myocardial relaxation |
dc.description.none.fl_txt_mv |
Contractility and relaxation measurements were combined with the determination of total phospholamban (PLB) phosphorylation and the immunodetection of PLB-phosphorylation sites in the intact, beating rat heart to identify the contributions of PLB phosphorylation at the Thr¹⁷ and Ser¹⁶ residues at different levels of β-adrenoceptor stimulation. Whereas with 30-300 nM isoproterenol, phosphorylation of Thr¹⁷, the Ca²⁺-calmodulin-dependent protein kinase-II (CaMKII) site and Ser¹⁶, the protein kinase A (PKA) site, contributed approximately 50% each to PLB phosphorylation, and both participated in the relaxant action of isoproterenol, at lower a level of β-adrenoceptor stimulation (isoproterenol 0.3-3 nM), both effects were exclusively due to Ser¹⁶ phosphorylation. Increasing [Ca]<sub>o</sub> at 3 nM isoproterenol, to obtain an increase in contractility comparable to that produced by 30 nM isoproterenol, significantly increased Thr¹⁷ phosphorylation and the relaxant effect produced by 3 nM isoproterenol. An increase in Thr¹⁷ phosphorylation and in the relaxant effect of 3 nM isoproterenol was also obtained by phosphatase inhibition (okadaic acid). In this case, Ser¹⁶ phosphorylation was also increased. Moreover, perfusion with 30 nM isoproterenol in the presence of the PKA inhibitor H-89 decreased phosphorylation at both PLB residues and diminished the inotropic and relaxant responses to the β-agonist. The relative contribution of Thr¹⁷ phosphorylation to the isoproterenol-induced phosphorylation of PLB and relaxation thus increased with the level of β-adrenoceptor stimulation and the consequent increase in PKA activity. The lack of Thr¹⁷ phosphorylation at low isoproterenol concentrations might therefore be attributed to a level of PKA activity insufficient to increase [Ca]<sub>i</sub> to activate the CaMKII system and/or to inhibit the phosphatase that dephosphorylates PLB. Centro de Investigaciones Cardiovasculares |
description |
Contractility and relaxation measurements were combined with the determination of total phospholamban (PLB) phosphorylation and the immunodetection of PLB-phosphorylation sites in the intact, beating rat heart to identify the contributions of PLB phosphorylation at the Thr¹⁷ and Ser¹⁶ residues at different levels of β-adrenoceptor stimulation. Whereas with 30-300 nM isoproterenol, phosphorylation of Thr¹⁷, the Ca²⁺-calmodulin-dependent protein kinase-II (CaMKII) site and Ser¹⁶, the protein kinase A (PKA) site, contributed approximately 50% each to PLB phosphorylation, and both participated in the relaxant action of isoproterenol, at lower a level of β-adrenoceptor stimulation (isoproterenol 0.3-3 nM), both effects were exclusively due to Ser¹⁶ phosphorylation. Increasing [Ca]<sub>o</sub> at 3 nM isoproterenol, to obtain an increase in contractility comparable to that produced by 30 nM isoproterenol, significantly increased Thr¹⁷ phosphorylation and the relaxant effect produced by 3 nM isoproterenol. An increase in Thr¹⁷ phosphorylation and in the relaxant effect of 3 nM isoproterenol was also obtained by phosphatase inhibition (okadaic acid). In this case, Ser¹⁶ phosphorylation was also increased. Moreover, perfusion with 30 nM isoproterenol in the presence of the PKA inhibitor H-89 decreased phosphorylation at both PLB residues and diminished the inotropic and relaxant responses to the β-agonist. The relative contribution of Thr¹⁷ phosphorylation to the isoproterenol-induced phosphorylation of PLB and relaxation thus increased with the level of β-adrenoceptor stimulation and the consequent increase in PKA activity. The lack of Thr¹⁷ phosphorylation at low isoproterenol concentrations might therefore be attributed to a level of PKA activity insufficient to increase [Ca]<sub>i</sub> to activate the CaMKII system and/or to inhibit the phosphatase that dephosphorylates PLB. |
publishDate |
2002 |
dc.date.none.fl_str_mv |
2002-08 |
dc.type.none.fl_str_mv |
info:eu-repo/semantics/article info:eu-repo/semantics/publishedVersion Articulo http://purl.org/coar/resource_type/c_6501 info:ar-repo/semantics/articulo |
format |
article |
status_str |
publishedVersion |
dc.identifier.none.fl_str_mv |
http://sedici.unlp.edu.ar/handle/10915/144219 |
url |
http://sedici.unlp.edu.ar/handle/10915/144219 |
dc.language.none.fl_str_mv |
spa |
language |
spa |
dc.relation.none.fl_str_mv |
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dc.rights.none.fl_str_mv |
info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International (CC BY 4.0) |
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openAccess |
rights_invalid_str_mv |
http://creativecommons.org/licenses/by/4.0/ Creative Commons Attribution 4.0 International (CC BY 4.0) |
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application/pdf 801-809 |
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