IQUIFIB   02644
INSTITUTO DE QUIMICA Y FISICOQUIMICA BIOLOGICAS "PROF. ALEJANDRO C. PALADINI"
Unidad Ejecutora - UE
artículos
Título:
Heteromerization Between the Bradykinin B2 Receptor and the Angiotensin-(1?7) Mas Receptor
Autor/es:
CERRATO BD; GRECCO HE; JANIC B; CARRETERO OA; GIRONACCIO MM
Revista:
HYPERTENSION
Editorial:
LIPPINCOTT WILLIAMS & WILKINS
Referencias:
Lugar: Philadelphia; Año: 2016
ISSN:
0194-911X
Resumen:
Bradykinin B2 receptor (B2R) and angiotensin-(1?7) Mas receptor (MasR)?mediated effects arephysiologically interconnected. The molecular basis for such cross talk is unknown. It is hypothesized that thecross talk occurs at the receptor level. We investigated B2R?MasR heteromerization and the functional consequencesof such interaction. B2R fused to the cyan uorescent protein and MasR fused to the yellow uorescent proteinwere transiently coexpressed in human embryonic kidney293T cells. Fluorescence resonance energy transferanalysis showed that B2R and MasR formed a constitutive heteromer, which was not modi ed by their agonists.B2R or MasR antagonists decreased uorescence resonance energy transfer ef ciency, suggesting that the antagonistpromoted heteromer dissociation. B2R?MasR heteromerization induced an 8-fold increase in the MasR ligand-binding af nity. On agonist stimulation, the heteromer was internalized into early endosomes with a slowersequestration rate from the plasma membrane, compared with single receptors. B2R?MasR heteromerizationinduced a greater increase in arachidonic acid release and extracellular signal?regulated kinase phosphorylationafter angiotensin-(1?7) stimulation, and this effect was blocked by the B2R antagonist. Concerning serine/threonine kinase Akt activity, a signi cant bradykinin-promoted activation was detected in B2R?MasR but not inB2R-expressing cells. Angiotensin-(1?7) and bradykinin elicited antiproliferative effects only in cells expressingB2R?MasR heteromers, but not in cells expressing each receptor alone. Proximity ligation assay con rmed B2R?MasR interaction in human glomerular endothelial cells supporting the interaction between both receptors in vivo.Our ndings 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-l?asting protective properties.