Functions of the plasminogen receptor Plg‐RKT

Plg‐RKT is a structurally unique transmembrane plasminogen receptor with both N‐ and C‐terminal domains exposed on the extracellular face of the cell. Its C‐terminal lysine functions to tether plasminogen to cell surfaces. Overexpression of Plg‐RKT increases cell surface plasminogen binding capacity while genetic deletion of Plg‐RKT decreases plasminogen binding. Plasminogen binding to Plg‐RKT results in promotion of plasminogen activation to the broad spectrum serine protease plasmin. This function is promoted by the physical association of Plg‐RKT with the urokinase receptor (uPAR). Plg‐RKT is broadly expressed in cells and tissues throughout the organism and its sequence is remarkably conserved phylogenetically. Plg‐RKT also is required for lactation and, thus, is necessary for survival of the species. This review provides an overview of established and emerging functions of Plg‐RKT and highlights major roles for Plg‐RKT in both the initiation and resolution of inflammation. While the roles for Plg‐RKT in the inflammatory response are predominantly plasmin(ogen)‐dependent, its role in lactation requires both plasminogen‐dependent and plasminogen‐independent mechanisms. Furthermore, the functions of Plg‐RKT are dependent on sex. In view of the broad tissue distribution of Plg‐RKT, its role in a broad array of physiological and pathological processes should provide a fruitful area for future investigation.