The Sarco(endo)plasmic-reticulum (SER) regulatory protein, Phospholamban (PLB), is a small, plasma membrane-associated protein found in the SER of cardiac, smooth and slow-twitch muscle. Believed to assemble into a pentamer, PLB regulates cardiac contractility and Ca2+ affinity for cardiac SER Ca2+ ATPase (SERCA2a). Non-phosphorylated PLB associates with SERCA2a, and inhibits Ca2+ reuptake into the SER. PLB activation occurs when key Serine/Threonine residues in PLB (Ser-10, Ser-16, Thr-17) are phosphorylated by numerous effectors, which include PKC, PKA, PKG, and CaM kinase. Phosphorylation of PLB causes dissociation from SERCA2a and a subsequent increase in the rate of Ca2+ reuptake into the SER, which accelerates ventricular relaxation.
