uPAuPAR

uPA-uPAR refers to the functional system formed by urokinase-type plasminogen activator (uPA) and its cell-surface receptor uPAR. The interaction localizes proteolytic activity to the vicinity of the cell, promoting pericellular proteolysis, ECM remodeling, and tissue remodeling in development, wound healing, and immune responses.

uPAR is a glycosylphosphatidylinositol-anchored receptor composed of three LU (Ly-6/uPAR) domains on the cell surface, lacking a transmembrane domain. uPA is a serine protease that exists as a single-chain zymogen and becomes active upon proteolytic processing. When uPA binds to uPAR, it concentrates the conversion of plasminogen to plasmin at the cell surface. Plasmin can directly degrade extracellular matrix components and activate matrix metalloproteinases, amplifying pericellular proteolysis and cell migration.

Beyond proteolysis, uPAR participates in signaling through interactions with integrins and other receptors, despite its GPI attachment. This cross-talk can influence cell adhesion, migration, survival, and angiogenesis, integrating proteolytic activity with signaling pathways such as MAPK and PI3K.

Soluble forms of uPAR (suPAR) arise from cleavage or shedding and circulate in body fluids. suPAR levels are studied as biomarkers in infection, inflammation, kidney disease, and cancer, reflecting immune activation and disease severity.

Clinical interest in the uPA-uPAR axis includes its role in cancer invasion and metastasis, inflammatory disorders, and fibrotic diseases. Therapeutic approaches target either uPA activity or uPAR interactions to modulate pericellular proteolysis and associated signaling.