Functions of the plasminogen receptor Plg-R_KT

Plg-R_KT 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-R_KT increases cell surface plasminogen binding capacity while genetic deletion of Plg-R_KT decreases plasminogen binding. Plasminogen binding to Plg-R_KT results in promotion of plasminogen activation to the broad spectrum serine protease plasmin. This function is promoted by the physical association of Plg-R_KT with the urokinase receptor (uPAR). Plg-R_KT is broadly expressed in cells and tissues throughout the organism and its sequence is remarkably conserved phylogenetically. Plg-R_KT 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-R_KT and highlights major roles for Plg-R_KT in both the initiation and resolution of inflammation. While the roles for Plg-R_KT 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-R_KT are dependent on sex. In view of the broad tissue distribution of Plg-R_KT , its role in a broad array of physiological and pathological processes should provide a fruitful area for future investigation.