Abstract
The sarcoplasmic reticulum (SR) Ca2+-ATPase (SERCA2a) is under the control of an SR protein named phospholamban (PLN). Dephosphorylated PLN inhibits SERCA2a, whereas phosphorylation of PLN at either the Ser16 site by PKA or the Thr17 site by CaMKII reverses this inhibition, thus increasing SERCA2a activity and the rate of Ca2+ uptake by the SR. This leads to an increase in the velocity of relaxation, SR Ca2+ load and myocardial contractility. In the intact heart, beta-adrenoceptor stimulation results in phosphorylation of PLN at both Ser16 and Thr17 residues. Phosphorylation of the Thr17 residue requires both stimulation of the CaMKII signaling pathways and inhibition of PP1, the major phosphatase that dephosphorylates PLN. These two prerequisites appear to be fulfilled by beta-adrenoceptor stimulation, which as a result of PKA activation, triggers the activation of CaMKII by increasing intracellular Ca2+, and inhibits PP1. Several pathological situations such as ischemia-reperfusion injury or hypercapnic acidosis provide the required conditions for the phosphorylation of the Thr17 residue of PLN, independently of the increase in PKA activity, i.e., increased intracellular Ca2+ and acidosis-induced phosphatase inhibition. Our r...Continue Reading
References
Feb 1, 1977·Circulation Research·A Fabiato, F Fabiato
Nov 1, 1978·The Journal of General Physiology·A Fabiato, F Fabiato
Oct 1, 1975·The Journal of Clinical Investigation·G R HeyndrickxS F Vatner
Apr 1, 1992·Journal of Molecular and Cellular Cardiology·R NapolitanoA Mattiazzi
Mar 28, 1991·European Journal of Biochemistry·L K MacDougallP Cohen
Aug 1, 1990·Journal of Applied Physiology·J D BrofmanS R White
Oct 1, 1989·Journal of Molecular and Cellular Cardiology·U LimbrunoM Mariani
Nov 2, 1989·Nature·P JamesE Carafoli
Aug 1, 1989·Circulation Research·S M KrauseL C Becker
Aug 1, 1986·Journal of Molecular and Cellular Cardiology·S T RapundaloJ J Feher
Nov 1, 1987·Basic Research in Cardiology·C Mundiña de WeilenmannA Mattiazzi
Mar 1, 1987·The Journal of Clinical Investigation·H KusuokaE Marban
Dec 1, 1981·Circulation Research·L M BilezikjianA Schwartz
Dec 1, 1982·Circulation·E Braunwald, R A Kloner
Jan 1, 1996·The American Journal of Physiology·C Mundiña-WeilenmannC H Orchard
Aug 1, 1996·Journal of Molecular and Cellular Cardiology·R ZucchiA Barsotti
Dec 27, 1996·The Journal of Biological Chemistry·C Mundiña-WeilenmannA Mattiazzi
Mar 21, 1998·The Journal of Biological Chemistry·W LuoE G Kranias
May 23, 1998·The Journal of Biological Chemistry·L VittoneA Mattiazzi
Apr 30, 1999·Physiological Reviews·R Bolli, E Marbán
Sep 16, 2000·The Journal of Biological Chemistry·G ChuE G Kranias
Jan 29, 2002·Journal of Molecular and Cellular Cardiology·Leticia VittoneAlicia Mattiazzi
Feb 6, 2002·Cardiovascular Research·Riccardo ZucchiG Paul Matherne
Oct 2, 2002·Pflügers Archiv : European journal of physiology·Matilde SaidAlicia Mattiazzi
May 24, 2003·American Journal of Physiology. Heart and Circulatory Physiology·M SaidA Mattiazzi
Jan 22, 2004·Journal of Molecular and Cellular Cardiology·J DeSantiagoD M Bers
Mar 17, 2005·Cardiovascular Research·Cecilia Mundiña-WeilenmannAlicia Mattiazzi
Mar 17, 2005·Cardiovascular Research·Y AbdallahC Schäfer
Aug 1, 1880·The Journal of Physiology·W H Gaskell
Citations
Oct 29, 2014·Canadian Journal of Physiology and Pharmacology·Dalia El-AniAsher Shainberg
Feb 3, 2015·Cell·Douglas M AndersonEric N Olson
Jan 28, 2015·Life Sciences·Aurélia Araújo FernandesIvanita Stefanon
Jul 3, 2010·Regulatory Peptides·Rosa MazzaBruno Tota
Jul 17, 2012·Journal of Molecular and Cellular Cardiology·Yiming WuMark E Anderson
Jul 16, 2014·Cardiovascular Research·Javier InserteDavid Garcia-Dorado
Dec 8, 2016·Science Signaling·Douglas M AndersonEric N Olson
Jul 17, 2012·Pharmacology·Da-Wei ZhangDi Yang
Jan 23, 2008·Acta Physiologica·T AngeloneM C Cerra
Nov 17, 2007·Cardiovascular Research·An Van den BerghPaul Herijgers
Feb 5, 2008·American Journal of Physiology. Lung Cellular and Molecular Physiology·Venkatachalem SathishGary C Sieck
Oct 17, 2008·Physiological Reviews·Jennifer DavisJoseph M Metzger
Aug 28, 2016·Fundamental & Clinical Pharmacology·Lei LiMenbayaer Tu
Feb 18, 2017·Circulation. Heart Failure·Bo ZhangRichard J Gumina
Nov 14, 2012·The Journal of Biological Chemistry·Emily M SchulzDavid F Wieczorek
Oct 3, 2007·The Journal of Biological Chemistry·Kim N HaGianluigi Veglia
Dec 15, 2019·Journal of Molecular and Cellular Cardiology·Maria J BaierAdam G Rokita
Aug 28, 2020·Journal of Molecular and Cellular Cardiology·Janet R ManningJo El J Schultz
Jul 12, 2021·The Journal of Nutritional Biochemistry·Yu-Shun LinPei-Min Chao