Heteromerization between the Bradykinin B2 Receptor and the Angiotensin-(1-7) Mas Receptor: Functional Consequences

Bradykinin B2 receptor (B2R) and angiotensin-(1-7) Mas receptor (MasR)-mediated effects are physiologically interconnected. The molecular basis for such cross talk is unknown. It is hypothesized that the cross talk occurs at the receptor level. We investigated B2R-MasR heteromerization and the funct...

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Autores principales:	Cerrato, B.D., Carretero, O.A., Janic, B., Grecco, H.E., Gironacci, M.M.
Formato:	JOUR
Materias:	B2 receptor heteromerization Mas receptor angiotensin[1-7] arachidonic acid bradykinin bradykinin B2 receptor cyan fluorescent protein mitogen activated protein kinase protein serine threonine kinase yellow fluorescent protein angiotensin I angiotensin I (1-7) bradykinin B2 receptor antagonist peptide fragment antiproliferative activity Article binding affinity cell membrane controlled study dissociation embryo endosome enzyme activity enzyme phosphorylation fluorescence resonance energy transfer HEK293 cell line human human cell priority journal protein protein interaction signal transduction analysis of variance animal cell culture drug effects genetic transfection metabolism physiology rat renin angiotensin aldosterone system sensitivity and specificity Analysis of Variance Angiotensin I Animals Bradykinin B2 Receptor Antagonists Cell Membrane Cells, Cultured Extracellular Signal-Regulated MAP Kinases HEK293 Cells Humans Peptide Fragments Rats Receptor Cross-Talk Receptor, Bradykinin B2 Renin-Angiotensin System Sensitivity and Specificity Transfection
Acceso en línea:	http://hdl.handle.net/20.500.12110/paper_0194911X_v68_n4_p1039_Cerrato
Aporte de:	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA) de Universidad de Buenos Aires

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spelling	todo:paper_0194911X_v68_n4_p1039_Cerrato2023-10-03T15:09:16Z Heteromerization between the Bradykinin B2 Receptor and the Angiotensin-(1-7) Mas Receptor: Functional Consequences Cerrato, B.D. Carretero, O.A. Janic, B. Grecco, H.E. Gironacci, M.M. B2 receptor heteromerization Mas receptor angiotensin[1-7] arachidonic acid bradykinin bradykinin B2 receptor cyan fluorescent protein mitogen activated protein kinase protein serine threonine kinase yellow fluorescent protein angiotensin I angiotensin I (1-7) bradykinin B2 receptor bradykinin B2 receptor antagonist mitogen activated protein kinase peptide fragment antiproliferative activity Article binding affinity cell membrane controlled study dissociation embryo endosome enzyme activity enzyme phosphorylation fluorescence resonance energy transfer HEK293 cell line human human cell priority journal protein protein interaction signal transduction analysis of variance animal cell culture drug effects genetic transfection metabolism physiology rat renin angiotensin aldosterone system sensitivity and specificity Analysis of Variance Angiotensin I Animals Bradykinin B2 Receptor Antagonists Cell Membrane Cells, Cultured Extracellular Signal-Regulated MAP Kinases HEK293 Cells Humans Peptide Fragments Rats Receptor Cross-Talk Receptor, Bradykinin B2 Renin-Angiotensin System Sensitivity and Specificity Transfection Bradykinin B2 receptor (B2R) and angiotensin-(1-7) Mas receptor (MasR)-mediated effects are physiologically interconnected. The molecular basis for such cross talk is unknown. It is hypothesized that the cross talk occurs at the receptor level. We investigated B2R-MasR heteromerization and the functional consequences of such interaction. B2R fused to the cyan fluorescent protein and MasR fused to the yellow fluorescent protein were transiently coexpressed in human embryonic kidney293T cells. Fluorescence resonance energy transfer analysis showed that B2R and MasR formed a constitutive heteromer, which was not modified by their agonists. B2R or MasR antagonists decreased fluorescence resonance energy transfer efficiency, suggesting that the antagonist promoted heteromer dissociation. B2R-MasR heteromerization induced an 8-fold increase in the MasR ligand-binding affinity. On agonist stimulation, the heteromer was internalized into early endosomes with a slower sequestration rate from the plasma membrane, compared with single receptors. B2R-MasR heteromerization induced a greater increase in arachidonic acid release and extracellular signal-regulated kinase phosphorylation after angiotensin-(1-7) stimulation, and this effect was blocked by the B2R antagonist. Concerning serine/threonine kinase Akt activity, a significant bradykinin-promoted activation was detected in B2R-MasR but not in B2R-expressing cells. Angiotensin-(1-7) and bradykinin elicited antiproliferative effects only in cells expressing B2R-MasR heteromers, but not in cells expressing each receptor alone. Proximity ligation assay confirmed B2R-MasR interaction in human glomerular endothelial cells supporting the interaction between both receptors in vivo. Our findings provide an explanation for the cross talk between bradykinin B2R and angiotensin-(1-7) MasR-mediated effects. B2R-MasR heteromerization induces functional changes in the receptor that may lead to long-lasting protective properties. © 2016 American Heart Association, Inc. Fil:Grecco, H.E. Universidad de Buenos Aires. Facultad de Ciencias Exactas y Naturales; Argentina. JOUR info:eu-repo/semantics/openAccess http://creativecommons.org/licenses/by/2.5/ar http://hdl.handle.net/20.500.12110/paper_0194911X_v68_n4_p1039_Cerrato
institution	Universidad de Buenos Aires
institution_str	I-28
repository_str	R-134
collection	Biblioteca Digital - Facultad de Ciencias Exactas y Naturales (UBA)
topic	B2 receptor heteromerization Mas receptor angiotensin[1-7] arachidonic acid bradykinin bradykinin B2 receptor cyan fluorescent protein mitogen activated protein kinase protein serine threonine kinase yellow fluorescent protein angiotensin I angiotensin I (1-7) bradykinin B2 receptor bradykinin B2 receptor antagonist mitogen activated protein kinase peptide fragment antiproliferative activity Article binding affinity cell membrane controlled study dissociation embryo endosome enzyme activity enzyme phosphorylation fluorescence resonance energy transfer HEK293 cell line human human cell priority journal protein protein interaction signal transduction analysis of variance animal cell culture drug effects genetic transfection metabolism physiology rat renin angiotensin aldosterone system sensitivity and specificity Analysis of Variance Angiotensin I Animals Bradykinin B2 Receptor Antagonists Cell Membrane Cells, Cultured Extracellular Signal-Regulated MAP Kinases HEK293 Cells Humans Peptide Fragments Rats Receptor Cross-Talk Receptor, Bradykinin B2 Renin-Angiotensin System Sensitivity and Specificity Transfection
spellingShingle	B2 receptor heteromerization Mas receptor angiotensin[1-7] arachidonic acid bradykinin bradykinin B2 receptor cyan fluorescent protein mitogen activated protein kinase protein serine threonine kinase yellow fluorescent protein angiotensin I angiotensin I (1-7) bradykinin B2 receptor bradykinin B2 receptor antagonist mitogen activated protein kinase peptide fragment antiproliferative activity Article binding affinity cell membrane controlled study dissociation embryo endosome enzyme activity enzyme phosphorylation fluorescence resonance energy transfer HEK293 cell line human human cell priority journal protein protein interaction signal transduction analysis of variance animal cell culture drug effects genetic transfection metabolism physiology rat renin angiotensin aldosterone system sensitivity and specificity Analysis of Variance Angiotensin I Animals Bradykinin B2 Receptor Antagonists Cell Membrane Cells, Cultured Extracellular Signal-Regulated MAP Kinases HEK293 Cells Humans Peptide Fragments Rats Receptor Cross-Talk Receptor, Bradykinin B2 Renin-Angiotensin System Sensitivity and Specificity Transfection Cerrato, B.D. Carretero, O.A. Janic, B. Grecco, H.E. Gironacci, M.M. Heteromerization between the Bradykinin B2 Receptor and the Angiotensin-(1-7) Mas Receptor: Functional Consequences
topic_facet	B2 receptor heteromerization Mas receptor angiotensin[1-7] arachidonic acid bradykinin bradykinin B2 receptor cyan fluorescent protein mitogen activated protein kinase protein serine threonine kinase yellow fluorescent protein angiotensin I angiotensin I (1-7) bradykinin B2 receptor bradykinin B2 receptor antagonist mitogen activated protein kinase peptide fragment antiproliferative activity Article binding affinity cell membrane controlled study dissociation embryo endosome enzyme activity enzyme phosphorylation fluorescence resonance energy transfer HEK293 cell line human human cell priority journal protein protein interaction signal transduction analysis of variance animal cell culture drug effects genetic transfection metabolism physiology rat renin angiotensin aldosterone system sensitivity and specificity Analysis of Variance Angiotensin I Animals Bradykinin B2 Receptor Antagonists Cell Membrane Cells, Cultured Extracellular Signal-Regulated MAP Kinases HEK293 Cells Humans Peptide Fragments Rats Receptor Cross-Talk Receptor, Bradykinin B2 Renin-Angiotensin System Sensitivity and Specificity Transfection
description	Bradykinin B2 receptor (B2R) and angiotensin-(1-7) Mas receptor (MasR)-mediated effects are physiologically interconnected. The molecular basis for such cross talk is unknown. It is hypothesized that the cross talk occurs at the receptor level. We investigated B2R-MasR heteromerization and the functional consequences of such interaction. B2R fused to the cyan fluorescent protein and MasR fused to the yellow fluorescent protein were transiently coexpressed in human embryonic kidney293T cells. Fluorescence resonance energy transfer analysis showed that B2R and MasR formed a constitutive heteromer, which was not modified by their agonists. B2R or MasR antagonists decreased fluorescence resonance energy transfer efficiency, suggesting that the antagonist promoted heteromer dissociation. B2R-MasR heteromerization induced an 8-fold increase in the MasR ligand-binding affinity. On agonist stimulation, the heteromer was internalized into early endosomes with a slower sequestration rate from the plasma membrane, compared with single receptors. B2R-MasR heteromerization induced a greater increase in arachidonic acid release and extracellular signal-regulated kinase phosphorylation after angiotensin-(1-7) stimulation, and this effect was blocked by the B2R antagonist. Concerning serine/threonine kinase Akt activity, a significant bradykinin-promoted activation was detected in B2R-MasR but not in B2R-expressing cells. Angiotensin-(1-7) and bradykinin elicited antiproliferative effects only in cells expressing B2R-MasR heteromers, but not in cells expressing each receptor alone. Proximity ligation assay confirmed B2R-MasR interaction in human glomerular endothelial cells supporting the interaction between both receptors in vivo. Our findings provide an explanation for the cross talk between bradykinin B2R and angiotensin-(1-7) MasR-mediated effects. B2R-MasR heteromerization induces functional changes in the receptor that may lead to long-lasting protective properties. © 2016 American Heart Association, Inc.
format	JOUR
author	Cerrato, B.D. Carretero, O.A. Janic, B. Grecco, H.E. Gironacci, M.M.
author_facet	Cerrato, B.D. Carretero, O.A. Janic, B. Grecco, H.E. Gironacci, M.M.
author_sort	Cerrato, B.D.
title	Heteromerization between the Bradykinin B2 Receptor and the Angiotensin-(1-7) Mas Receptor: Functional Consequences
title_short	Heteromerization between the Bradykinin B2 Receptor and the Angiotensin-(1-7) Mas Receptor: Functional Consequences
title_full	Heteromerization between the Bradykinin B2 Receptor and the Angiotensin-(1-7) Mas Receptor: Functional Consequences
title_fullStr	Heteromerization between the Bradykinin B2 Receptor and the Angiotensin-(1-7) Mas Receptor: Functional Consequences
title_full_unstemmed	Heteromerization between the Bradykinin B2 Receptor and the Angiotensin-(1-7) Mas Receptor: Functional Consequences
title_sort	heteromerization between the bradykinin b2 receptor and the angiotensin-(1-7) mas receptor: functional consequences
url	http://hdl.handle.net/20.500.12110/paper_0194911X_v68_n4_p1039_Cerrato
work_keys_str_mv	AT cerratobd heteromerizationbetweenthebradykininb2receptorandtheangiotensin17masreceptorfunctionalconsequences AT carreterooa heteromerizationbetweenthebradykininb2receptorandtheangiotensin17masreceptorfunctionalconsequences AT janicb heteromerizationbetweenthebradykininb2receptorandtheangiotensin17masreceptorfunctionalconsequences AT greccohe heteromerizationbetweenthebradykininb2receptorandtheangiotensin17masreceptorfunctionalconsequences AT gironaccimm heteromerizationbetweenthebradykininb2receptorandtheangiotensin17masreceptorfunctionalconsequences
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Heteromerization between the Bradykinin B2 Receptor and the Angiotensin-(1-7) Mas Receptor: Functional Consequences

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