Urokinase plasminogen activator receptor (uPAR) - urokinase-type plasminogen activator (uPA) interaction interface (uPAR-uPA interface)

The urokinase plasminogen activator receptor (uPAR) – urokinase-type plasminogen activator (uPA) interaction interface is a critical regulatory node in the control of pericellular proteolysis and cell surface signaling (UniProt P14317, P00749). uPAR is a glycosylphosphatidylinositol (GPI)-anchored membrane protein that binds the serine protease uPA with high affinity, primarily through the growth factor-like domain (GFD) of uPA (PubMed: 25635305). This interaction localizes plasminogen activation to the cell surface, facilitating the degradation of the extracellular matrix (ECM) and promoting cell migration, invasion, and tissue remodeling (PubMed: 17607248). Beyond its proteolytic role, the uPAR-uPA complex acts as a signaling scaffold by interacting with co-receptors like integrins and vitronectin to trigger intracellular pathways such as MAPK/ERK and PI3K/Akt (PubMed: 21620143). In many cancers, uPAR is overexpressed and correlates with poor prognosis, as the interaction drives tumor metastasis and angiogenesis (PubMed: 23813802). Consequently, therapeutic strategies focus on disrupting this protein-protein interaction (PPI) using small molecules like IPR-803 or peptides like Å6 to inhibit tumor progression and spread (PubMed: 25635305, 15192009).

Other names

uPAR-uPA binding siteCD87-uPA interactionPLAUR-PLAU interaction interfaceuPAR-uPA complex

Competitive inhibition of the binding between the urokinase-type plasminogen activator (uPA) and its receptor (uPAR), thereby preventing the localization of proteolytic activity to the cell surface and inhibiting downstream intracellular signaling pathways (PubMed: 25635305).