Hkb. Simmerman et Lr. Jones, PHOSPHOLAMBAN - PROTEIN-STRUCTURE, MECHANISM OF ACTION, AND ROLE IN CARDIAC-FUNCTION, Physiological reviews, 78(4), 1998, pp. 921-947
A comprehensive discussion is presented of advances in understanding t
he structure and function of phospholamban (PLB), the principal regula
tor of the Ca2+-ATPase of cardiac sarcoplasmic reticulum. Extensive hi
storical studies are reviewed to provide perspective on recent develop
ments. Phospholamban gene structure, expression, and regulation are pr
esented in addition to in vitro and in vivo studies of PLB protein str
ucture and activity. Applications of breakthrough experimental technol
ogies in identifying PLB structure-function relationships and in defin
ing its interaction with the Ca2+-ATPase are also highlighted. The cur
rent leading viewpoint of PLB's mechanism of action emerges from a cri
tical examination of alternative hypotheses and the most recent experi
mental evidence. The potential physiological relevance of PLB function
in human heart failure is also covered. The interest in PLB across di
verse biochemical disciplines portends its continued intense scrutiny
and its potential exploitation as a therapeutic target.