PKA-mediated phosphorylation of the beta1-adrenergic receptor promotes Gs/Gi switching

Cellular Signalling
Negin P MartinR J Lefkowitz

Abstract

Recently, it has been shown that PKA-mediated phosphorylation of the beta(2)-adrenergic receptor (beta(2)-AR) by the cyclic AMP-dependent protein kinase (PKA) reduces its affinity for G(s) and increases its affinity for G(i). Here we demonstrate that, like the beta(2)-AR, the beta(1)-AR is also capable of "switching" its coupling from G(s) to G(i) in a PKA-dependent manner. The beta(1)-AR is capable of activating adenylate cyclase via G(s), and can also activate the extracellular-regulated kinases, p44 and p42 (ERK1/2). In transfected CHO cells, the observed beta(1)-AR-mediated activation of ERK is both sensitive to pertussis toxin (PTX), indicating involvement of G(i)/G(o), and to the PKA inhibitor, H-89. beta(1)-ARs with PKA phosphorylation sites mutated to alanines are unable to activate ERK. Mutating these same residues to aspartic acid, mimicking PKA phosphorylation, leads to a decrease in G(s)-stimulated cAMP accumulation and an increase in PTX-sensitive ERK activation. These results strongly support the hypothesis that the beta(1)-AR, like the beta(2)-AR, can undergo PKA-dependent "G(s)/G(i) switching".

References

Jun 1, 1983·Proceedings of the National Academy of Sciences of the United States of America·J M StadelR J Lefkowitz
Dec 1, 1993·Pharmacology & Therapeutics·O E Brodde
Apr 1, 1993·Proceedings of the National Academy of Sciences of the United States of America·R A CrucianiM H Makman
Nov 26, 1999·Circulation Research·R P XiaoE G Lakatta
Apr 12, 2000·Circulation·R J LefkowitzW J Koch
Feb 15, 2001·Proceedings of the National Academy of Sciences of the United States of America·W Z ZhuR P Xiao
Jan 24, 2002·Nature·Howard A RockmanRobert J Lefkowitz
Jan 29, 2003·Proceedings of the National Academy of Sciences of the United States of America·George S BaillieMiles D Houslay
May 2, 2003·The Journal of Biological Chemistry·Liaoyuan A HuRobert J Lefkowitz
Jun 7, 2003·Science·Yang Xiang, Brian K Kobilka
Sep 5, 2003·Proceedings of the National Academy of Sciences of the United States of America·Yang Xiang, Brian Kobilka
Oct 16, 2003·The Journal of Biological Chemistry·Gayathri SwaminathBrian K Kobilka

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Citations

Jan 13, 2011·Cardiovascular Drugs and Therapy·Ruduwaan SalieAmanda Lochner
May 3, 2008·Journal of Proteome Research·Cristian I RuseJohn R Yates
Sep 5, 2013·Molecular Therapy : the Journal of the American Society of Gene Therapy·Mohsin KhanMark A Sussman
Sep 22, 2010·Molecular Pharmacology·Chetan B PatelHoward A Rockman
Mar 15, 2012·American Journal of Physiology. Endocrinology and Metabolism·Hesham A Tawfeek, Abdul B Abou-Samra
Jun 19, 2013·Molecular Cancer·Christelle P El-HaibiJames W Lillard
May 4, 2012·The Journal of Neuroscience : the Official Journal of the Society for Neuroscience·Alex C Koon, Vivian Budnik
May 6, 2014·Trends in Pharmacological Sciences·Stefano Costanzi
Oct 24, 2007·Immunology·Maria MagocsiJudith Szelenyi
Sep 11, 2013·Wiley Interdisciplinary Reviews. Systems Biology and Medicine·Kim T Blackwell, Joanna Jedrzejewska-Szmek
Jan 15, 2015·The FEBS Journal·Elin NymanGunnar Cedersund
Feb 1, 2005·Life Sciences·Gaël Jean-BaptisteMichael T Greenwood
Oct 4, 2011·Journal of Receptor and Signal Transduction Research·Yoshio TanakaYoshitoshi Kasuya
Aug 29, 2006·Anais Da Academia Brasileira De Ciências·Patricia C BrumAlessandra Medeiros
Nov 24, 2017·Nature Communications·Jialu WangHoward A Rockman
Mar 23, 2017·Journal of Cardiovascular Pharmacology·Qin FuYang K Xiang
Jul 12, 2011·British Journal of Pharmacology·Mansoor N BangashRupert M Pearse
Mar 1, 2012·British Journal of Pharmacology·A Rietz, Jp Spiers
Sep 8, 2005·The Journal of Pharmacology and Experimental Therapeutics·Masaaki SatoRoger J Summers
Dec 23, 2008·Molecular Pharmacology·Eric GutknechtFrank M Dautzenberg
Jun 7, 2020·Proceedings of the National Academy of Sciences of the United States of America·Ali I KayaT M Iverson
Jan 26, 2007·The Journal of Biological Chemistry·Naresh KumarSheila Collins
Sep 4, 2007·American Journal of Physiology. Heart and Circulatory Physiology·Xiao-Hui ZhangJean-Pierre Bourreau
Jul 26, 2017·PLoS Computational Biology·Joanna Jȩdrzejewska-SzmekKim T Blackwell
Sep 1, 2007·Expert Review of Endocrinology & Metabolism·Maria Nesterova, Constantine A Stratakis
Jan 22, 2011·British Journal of Pharmacology·Bengt-Olof NilssonL M Fredrik Leeb-Lundberg

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