PHOSPHOLAMBAN - PROTEIN-STRUCTURE, MECHANISM OF ACTION, AND ROLE IN CARDIAC-FUNCTION

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.