PMID: 16648892May 2, 2006Paper

The importance of the Thr17 residue of phospholamban as a phosphorylation site under physiological and pathological conditions

Brazilian Journal of Medical and Biological Research = Revista Brasileira De Pesquisas Médicas E Biológicas
A MattiazziEvangelia G Kranias

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

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Citations

Jan 28, 2015·Life Sciences·Aurélia Araújo FernandesIvanita Stefanon
Jul 17, 2012·Journal of Molecular and Cellular Cardiology·Yiming WuMark E Anderson
Dec 8, 2016·Science Signaling·Douglas M AndersonEric N Olson
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
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

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