Publication Date:
2009-01-01
Description:
An agonist-occupiedβ2-adrenergic receptor (β2-AR) recruits G protein receptor kinase-2 (GRK2) which is recruited to the membrane. Thus, the physical proximity of activatedβ2-AR and PI-3K allows the activation of the latter. In contrast, it has been observed that theβ1-AR is unable to activate the PI-3K/Akt pathway. We hypothesized that the difference might be due to molecular determinants present in the carboxy termini of the twoβ-AR subtypes. Using transiently transfected HEK 293 cells expressing eitherβ1- orβ2-AR, we also observed that in presence of an agonist,β2-AR, but notβ1-AR, is able to activate the PI-3K/Akt pathway. Switching the seventh transmembrane domain and the carboxy tail between the two receptors reverses this phenotype; that is,β1×β2-AR can activate the PI-3K/Akt pathway whereasβ2×β1-AR cannot. Pretreatment with pertussis toxin abolished the activation of PI-3K byβ2- orβ1×β2-AR stimulation. Ligand-mediated internalization of theβ2-AR induced by a 15-minute stimulation with agonist was abolished in the presence of a dominant negative of PI-3K or following pertussis toxin pretreatment. These results indicate that the subtype-specific differences in the coupling to PI-3K/Akt pathway are due to molecular determinants present in the carboxy tail of the receptor and further thatβ2-AR activates PI-3K via a pertussis toxin-sensitive mechanism.
Print ISSN:
1687-8876
Electronic ISSN:
1687-8884
Topics:
Biology
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