cAMP-stimulated protein phosphatase 2A activity associated with muscle A kinase-anchoring protein (mAKAP) signaling complexes inhibits the phosphorylation and activity of the cAMP-specific phosphodiesterase PDE4D3.

The Journal of Biological Chemistry
Kimberly L Dodge-KafkaMichael S Kapiloff

Abstract

The concentration of the second messenger cAMP is tightly controlled in cells by the activity of phosphodiesterases. We have previously described how the protein kinase A-anchoring protein mAKAP serves as a scaffold for the cAMP-dependent protein kinase PKA and the cAMP-specific phosphodiesterase PDE4D3 in cardiac myocytes. PKA and PDE4D3 constitute a negative feedback loop whereby PKA-catalyzed phosphorylation and activation of PDE4D3 attenuate local cAMP levels. We now show that protein phosphatase 2A (PP2A) associated with mAKAP complexes is responsible for reversing the activation of PDE4D3 by catalyzing the dephosphorylation of PDE4D3 serine residue 54. Mapping studies reveal that a C-terminal mAKAP domain (residues 2085-2319) binds PP2A. Binding to mAKAP is required for PP2A function, such that deletion of the C-terminal domain enhances both base-line and forskolin-stimulated PDE4D3 activity. Interestingly, PP2A holoenzyme associated with mAKAP complexes in the heart contains the PP2A targeting subunit B56delta. Like PDE4D3, B56delta is a PKA substrate, and PKA phosphorylation of mAKAP-bound B56delta enhances phosphatase activity 2-fold in the complex. Accordingly, expression of a B56delta mutant that cannot be phosphoryl...Continue Reading

References

Oct 1, 1995·The Biochemical Journal·S Wera, B A Hemmings
Mar 14, 2000·Current Opinion in Cell Biology·D M Virshup
Mar 27, 2001·Annual Review of Pharmacology and Toxicology·S F Steinberg, L L Brunton
Dec 19, 2001·American Journal of Physiology. Heart and Circulatory Physiology·William H duBellTerry B Rogers
Aug 1, 2002·Nature Cell Biology·Andrea L Bauman, John D Scott
Feb 14, 2004·American Journal of Physiology. Heart and Circulatory Physiology·Qinghang Liu, Polly A Hofmann
Jun 9, 2004·The Biochemical Journal·Jennifer J Carlisle MichelJohn D Scott
Jan 18, 2005·Experimental Cell Research·Genevieve C PareMichael S Kapiloff
Mar 22, 2005·American Journal of Physiology. Heart and Circulatory Physiology·Marisa S GigenaTerry B Rogers
Dec 13, 2005·Molecular Cell·Jennifer J Carlisle MichelJohn D Scott
Feb 8, 2006·European Journal of Cell Biology·Kimberly L Dodge-Kafka, Michael S Kapiloff
Apr 29, 2006·Circulation Research·Kimberly L Dodge-KafkaJohn D Scott
Oct 14, 2006·Circulation Research·Rodolphe FischmeisterGrégoire Vandecasteele
Feb 16, 2007·Proceedings of the National Academy of Sciences of the United States of America·Jung-Hyuck AhnAngus C Nairn
Dec 26, 2008·Science Signaling·Wei WongJohn D Scott
Nov 4, 2009·Journal of Molecular and Cellular Cardiology·Jinliang LiMichael S Kapiloff

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Citations

Feb 1, 2012·Cell Research·Dries CastermansJohan M Thevelein
Oct 8, 2011·Journal of Cardiovascular Pharmacology·Riad Efendiev, Carmen W Dessauer
Nov 15, 2011·Journal of Cardiovascular Pharmacology·Graeme K Carnegie, Brian T Burmeister
May 13, 2011·Journal of Cardiovascular Pharmacology·John M Redden, Kimberly L Dodge-Kafka
Aug 23, 2011·American Journal of Physiology. Heart and Circulatory Physiology·Dario DivianiMichael S Kapiloff
Jul 9, 2011·Circulation Research·Yang K Xiang
Sep 22, 2012·Circulation Research·Jinliang LiMichael S Kapiloff
Apr 2, 2014·Nature Reviews. Drug Discovery·Donald H MauriceVincent C Manganiello
Oct 10, 2012·Annual Review of Pharmacology and Toxicology·John D ScottKjetil Taskén
Apr 8, 2014·Pharmacology & Therapeutics·Konstantinos Lefkimmiatis, Manuela Zaccolo
Mar 27, 2013·Trends in Cardiovascular Medicine·Qin FuYang K Xiang
Dec 7, 2010·Life Sciences·Terry S EltonDmitry Terentyev
Sep 20, 2015·Cellular Signalling·Alessandro DemaEnno Klussmann
Dec 1, 2015·Frontiers in Pharmacology·Silvio WeberAli El-Armouche
Jan 30, 2013·Biological Reviews of the Cambridge Philosophical Society·Juana M Gancedo
Apr 23, 2014·Fundamental & Clinical Pharmacology·Carolina OteroJuan E Jung
Jul 15, 2015·The Journal of Clinical Investigation·Gunnar HougeVeerle Janssens
Sep 21, 2013·Journal of Molecular and Cellular Cardiology·Jordi HeijmanDobromir Dobrev
Sep 21, 2011·Seminars in Cell & Developmental Biology·Helen V EdwardsGeorge S Baillie
May 24, 2011·Journal of Molecular and Cellular Cardiology·Michael D KritzerMichael S Kapiloff
Apr 24, 2012·Cellular Signalling·Jurgen VandammeJohan M Thevelein
Feb 26, 2016·Critical Reviews in Biochemistry and Molecular Biology·Nathan Wlodarchak, Yongna Xing
Sep 3, 2016·Journal of Molecular and Cellular Cardiology·Dmitry Terentyev, Shanna Hamilton
Nov 12, 2016·Journal of Molecular and Cellular Cardiology·Ellen R Lubbers, Peter J Mohler
Jan 26, 2018·Journal of Cardiovascular Development and Disease·Tanya A Baldwin, Carmen W Dessauer
Feb 21, 2018·Journal of Cardiovascular Development and Disease·Maria Ercu, Enno Klussmann
Mar 31, 2018·American Journal of Physiology. Heart and Circulatory Physiology·Santosh V SuryavanshiBradley K McConnell
Sep 9, 2017·Oncotarget·Haitao WangWenhua Zheng
Jan 1, 2015·Journal of Cardiovascular Pharmacology·Catherine L PassarielloMichael S Kapiloff
Dec 21, 2018·International Journal of Obesity : Journal of the International Association for the Study of Obesity·Tao TongTaesun Park
Dec 19, 2020·Pharmacological Reviews·Manuela ZaccoloMiguel J Lobo

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