Determinants Present in the Receptor Carboxy Tail Are Responsible for Differences in Subtype-Specific Coupling of β-Adrenergic Receptors to Phosphoinositide 3-Kinase
Source
International Journal of Cell Biology
Issue
Vol. 2009, Issue 2009 (31 Dec. 2009), pp.1-8, 8 p.
Publisher
Hindawi Publishing Corporation
Publication Date
2009-02-05
Country of Publication
Egypt
No. of Pages
8
Main Subjects
Abstract EN
An agonist-occupied β2-adrenergic receptor (β2-AR) recruits G protein receptor kinase-2 (GRK2) which is recruited to the membrane.
Thus, the physical proximity of activated β2-AR and PI-3K allows the activation of the latter.
In contrast, it has been observed that the β1-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 two β-AR subtypes.
Using transiently transfected HEK 293 cells expressing either β1- or β2-AR, we also observed that in presence of an agonist, β2-AR, but not β1-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 whereas β2×β1-AR cannot.
Pretreatment with pertussis toxin abolished the activation of PI-3K by β2- or β1×β2-AR stimulation.
Ligand-mediated internalization of the β2-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 that β2-AR activates PI-3K via a pertussis toxin-sensitive mechanism.
American Psychological Association (APA)
2009. Determinants Present in the Receptor Carboxy Tail Are Responsible for Differences in Subtype-Specific Coupling of β-Adrenergic Receptors to Phosphoinositide 3-Kinase. International Journal of Cell Biology،Vol. 2009, no. 2009, pp.1-8.
https://search.emarefa.net/detail/BIM-511499
Modern Language Association (MLA)
Determinants Present in the Receptor Carboxy Tail Are Responsible for Differences in Subtype-Specific Coupling of β-Adrenergic Receptors to Phosphoinositide 3-Kinase. International Journal of Cell Biology No. 2009 (2009), pp.1-8.
https://search.emarefa.net/detail/BIM-511499
American Medical Association (AMA)
Determinants Present in the Receptor Carboxy Tail Are Responsible for Differences in Subtype-Specific Coupling of β-Adrenergic Receptors to Phosphoinositide 3-Kinase. International Journal of Cell Biology. 2009. Vol. 2009, no. 2009, pp.1-8.
https://search.emarefa.net/detail/BIM-511499
Data Type
Journal Articles
Language
English
Notes
Includes bibliographical references
Record ID
BIM-511499