Signaling from beta(1)- and beta(2)-adrenergic receptors is defined by differential interactions with PDE4.

Signaling from beta(1)- and beta(2)-adrenergic receptors is defined by differential interactions with PDE4. Research Abstract Details 

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Signaling from beta(1)- and beta(2)-adrenergic receptors is defined by differential interactions with PDE4. Abstract Text:

Wito Richter,Peter Day,Rani Agrawal,Matthew D Bruss, Granier,Yvonne L Wang, Rasmussen,Kathleen Horner,Ping Wang,Tao Lei,Andrew J Patterson,Brian Kobilka,Marco Conti,Wito Richter,Peter Day,Rani Agrawal,Matthew D Bruss, Granier,Yvonne L Wang, Rasmussen,Kathleen Horner,Ping Wang,Tao Lei,Andrew J Patterson,Brian Kobilka,Marco Conti,Wito Richter,Peter Day,Rani Agrawal,Matthew D Bruss, Granier,Yvonne L Wang, Rasmussen,Kathleen Horner,Ping Wang,Tao Lei,Andrew J Patterson,Brian Kobilka,Marco Conti,

beta(1)- and beta(2)-adrenergic receptors (betaARs) are highly homologous, yet they play clearly distinct roles in cardiac physiology and pathology. Myocyte contraction, for instance, is readily stimulated by beta(1)AR but not beta(2)AR signaling, and chronic stimulation of the two receptors has opposing effects on myocyte apoptosis and cell survival. Differences in the assembly of macromolecular signaling complexes may explain the distinct biological outcomes. Here, we demonstrate that beta(1)AR forms a signaling complex with a cAMP-specific phosphodiesterase (PDE) in a manner inherently different from a beta(2)AR/beta-arrestin/PDE complex reported previously. The beta(1)AR binds a PDE variant, PDE4D8, in a direct manner, and occupancy of the receptor by an agonist causes dissociation of this complex. Conversely, agonist binding to the beta(2)AR is a prerequisite for the recruitment of a complex consisting of beta-arrestin and the PDE4D variant, PDE4D5, to the receptor. We propose that the distinct modes of interaction with PDEs result in divergent cAMP signals in the vicinity of the two receptors, thus, providing an additional layer of complexity to enforce the specificity of beta(1)- and beta(2)-adrenoceptor signaling.

Signaling from beta(1)- and beta(2)-adrenergic receptors is defined by differential interactions with PDE4. Publishing Authors By Initials

W Richter,P Day,R Agrawal,MD Bruss,S Granier,YL Wang,SG Rasmussen,K Horner,P Wang,T Lei,AJ Patterson,B Kobilka,M Conti,W Richter,P Day,R Agrawal,MD Bruss,S Granier,YL Wang,SG Rasmussen,K Horner,P Wang,T Lei,AJ Patterson,B Kobilka,M Conti,W Richter,P Day,R Agrawal,MD Bruss,S Granier,YL Wang,SG Rasmussen,K Horner,P Wang,T Lei,AJ Patterson,B Kobilka,M Conti,

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Signaling from beta(1)- and beta(2)-adrenergic receptors is defined by differential interactions with PDE4. Journal Published:

PUBLICATION TYPE: Journal Article

Journal: The EMBO journal

VOLUME: 27

Page Numbers: 384-93

Journal Abbreviation: EMBO J.

ISSN: 1460-2075

DAY: 10

MONTH: 01

YEAR: 2008

Signaling from beta(1)- and beta(2)-adrenergic receptors is defined by differential interactions with PDE4. Information

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LANGUAGE: eng

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Grant and Affiliation Information for Signaling from beta(1)- and beta(2)-adrenergic receptors is defined by differential interactions with PDE4.

AFFILIATION: Division of Reproductive Biology, Department of Obstetrics and Gynecology, Stanford University School of Medicine, Stanford, CA, USA.

Country: England

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MEDLINETA: EMBO J

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