Functional domains of the mouse beta(3)-adrenoceptor associated with differential G-protein coupling.

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Functional domains of the mouse beta(3)-adrenoceptor associated with differential G-protein coupling. Abstract Text:

M Sato,D S Hutchinson,B A Evans,R J Summers,M Sato,D S Hutchinson,B A Evans,R J Summers,

Localization of G-protein-coupled receptors within membrane microdomains is associated with differential signalling pathway activation. We have shown that two mouse beta(3)-AR (beta(3)-adrenoceptor) isoforms encoded by alternatively spliced mRNAs differ in their signalling properties; the beta(3a)-AR couples only with G(s), whereas the beta(3b)-AR couples with both G(s) and G(i). Our previous studies indicated that the beta(3a)-AR is restrained from coupling with G(i) due to the interaction of residues in the C-terminus with other protein(s). We have investigated the hypothesis that the beta(3a)-AR interacts with caveolin. Disruption of caveolae in CHO (Chinese-hamster ovary)-K1 cells expressing wild-type beta(3a)-ARs with filipin III, or mutation of a putative caveolin-binding site in the beta(3a)-AR, causes cAMP accumulation to become PTX (pertussis toxin)-sensitive. Likewise, filipin treatment of mouse brown adipocytes that express endogenous beta(3a)-ARs produces a substantial reduction in agonist-stimulated cAMP production that is rescued by pre-treatment with PTX. These studies suggest that beta(3a)-ARs may be restricted to caveolae and that localization of the receptor may play a specific role in G-protein-mediated signalling.

Functional domains of the mouse beta(3)-adrenoceptor associated with differential G-protein coupling. Publishing Authors By Initials

M Sato,DS Hutchinson,BA Evans,RJ Summers,M Sato,DS Hutchinson,BA Evans,RJ Summers,

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Functional domains of the mouse beta(3)-adrenoceptor associated with differential G-protein coupling. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: Biochemical Society transactions

VOLUME: 35

Page Numbers: 1035-7

Journal Abbreviation: Biochem. Soc. Trans.

ISSN: 0300-5127

DAY: 24

MONTH: Nov

YEAR: 2007

Functional domains of the mouse beta(3)-adrenoceptor associated with differential G-protein coupling. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Functional domains of the mouse beta(3)-adrenoceptor associated with differential G-protein coupling.

AFFILIATION: Department of Pharmacology, Monash University, Clayton, VIC 3800, Australia.

Country: England

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MEDLINETA: Biochem Soc Trans

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