TARGETING OF TISSUE-PLASMINOGEN ACTIVATOR TO THE REGULATED PATHWAY OFSECRETION

Tissue plasminogen activator is a serine protease that plays the domin ant role in removal of fibrin from the vascular tree by activating pla sminogen to the primary fibrinolytic enzyme, plasmin. Tissue plasminog en activator has a widespread neuroendocrine distribution in addition to its expression by endothelial cells. Within neuroendocrine cells se cretory proteins are sorted into one of two pathways: regulated or con stitutive. Proteins entering the regulated pathway are concentrated an d stored in vesicles, and subsequently released upon stimulation by a secretagogue. In contrast, in the constitutive pathway, newly synthesi zed protein is not stored but is transported directly to the cell surf ace and secreted even in the absence of an extracellular signal. The f ocus of this article is to review recent studies demonstrating that ti ssue plasminogen activator is targeted to the regulated secretory path way in neuroendocrine cells and to discuss the physiological implicati ons of the trafficking of tissue plasminogen activator to regulated se cretory vesicles. (Trends Cardiovasc Med 1998;8:306-312) (C) 1998, Els evier Science Inc.