Role of Phospholamban Phosphorylation on Thr17 in physiologic and pathologic conditions

MATTIAZZI A,; MUNDIÑA-WEILENMANN C,; CHU G,; VITTONE L,; KRANIAS E

CARDIOVASCULAR RESEARCH

Elsevier Science B.V.

Lugar: Amsterdam; Año: 2005 vol. 68 p. 366 - 375

0008-6363

The sarcoplasmic reticulum (SR) Ca(2+)-ATPase (SERCA2a) is under the control of a closely associated SR protein named phospholamban (PLN). Dephosphorylated PLN inhibits the SR Ca(2+) pump, whereas phosphorylation of PLN, at either Ser(16) by PKA or Thr(17) by calmodulin-dependent protein kinase II (CaMKII), reverses this inhibition, thus increasing SERCA2a activity and the rate of Ca(2+) uptake by the SR. This would in turn lead to an increase in the velocity of relaxation, SR Ca(2+) load, and myocardial contractility. Thus, PLN is a major determinant of cardiac contractility and relaxation. Although in the intact heart, beta-adrenoceptor stimulation results in phosphorylation of PLN at both Ser(16) and Thr(17) residues, the role of Thr(17) site has long remained equivocal. In this review, we attempt to highlight the signaling cascade and the physiological relevance of the phosphorylation of this residue in the heart under both physiological and pathological situations.