Biologically active, non membrane‐anchored precursors – an overview

Peptides function as chemical signals between cells of multicellular organisms via specific receptors on target cells. Many hormones, neuromodulators and growth factors are peptides. Peptide hormones and other biologically active peptides are synthesized as higher molecular weight precursor proteins (pro‐hormones), which must undergo post‐translational modification to yield the bioactive peptide(s). In many instances, more than one biologically active peptide is generated from one and the same precursor. In most cases, these precursors are biologically inert and their existence is confined to the membrane‐enclosed subcellular compartments where processing of the pro‐hormones takes place. A class of growth factors that derive from membrane‐anchored precursors which themselves are biologically active constitute an exception to this model. The list of the membrane‐anchored biologically active precursors has been the subject of specialized reviews. The present review focuses on precursors other than membrane‐anchored precursors, which were found to be biologically active and which often display different biological activities, and may mediate their effects via receptors independent from those of their generated peptides.