Endothelial β2 adrenergic signaling to AKT: Role of Gi and SRC

Michele Ciccarelli, Ersilia Cipolletta, Gaetano Santulli, Alfonso Campanile, Kevin Pumiglia, Pasquale Cervero, Lucio Pastore, Dalila Astone, Bruno Trimarco, Guido Iaccarino

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43 Scopus citations

Abstract

We have recently demonstrated that endothelial β2 adrenergic receptors (β2AR) regulate eNOS activity and consequently vascular tone, through means of PKB/AKT. In this work we explored the signal transduction pathway leading to AKT/eNOS activation in endothelial cells (EC). Using pharmacological and molecular inhibitors both in cultured EC cells and in ex vivo rat carotid preparations, we found that Gi coupling of the β2AR is needed for AKT activation and vasorelaxation. Since endothelial activation is sensitive to pertussis toxin but not to Giβγ inhibition by βARKct, we conclude that Gαi mediates βAR induced AKT activation. Downstream, βAR signalling requires the soluble tyrosine kinase SRC, as both in cultured EC and rat carotid, the mutant dominant negative of SRC prevent β2AR induced endothelial activation and vasodilation. In EC, Gαi directly interacts with SRC and this interaction leads to SRC activation and phosphorylation in a manner that is regulated by β2AR stimulation. We propose a novel signal transduction pathway for β2AR stimulation trough Gαi and SRC, leading to activation of AKT.

Original languageEnglish (US)
Pages (from-to)1949-1955
Number of pages7
JournalCellular Signalling
Volume19
Issue number9
DOIs
StatePublished - Sep 1 2007

Keywords

  • Endothelium
  • G protein
  • Molecular biology
  • Receptors
  • Vascular biology

ASJC Scopus subject areas

  • Cell Biology

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    Ciccarelli, M., Cipolletta, E., Santulli, G., Campanile, A., Pumiglia, K., Cervero, P., Pastore, L., Astone, D., Trimarco, B., & Iaccarino, G. (2007). Endothelial β2 adrenergic signaling to AKT: Role of Gi and SRC. Cellular Signalling, 19(9), 1949-1955. https://doi.org/10.1016/j.cellsig.2007.05.007