Title: Is uPAR the Centre of a Sensing System Involved in the Regulation of Inflammation?
Volume: 2
Issue: 3
Author(s): Bernard Degryse
Affiliation:
Keywords:
inflammation, urokinase receptor, urokinase, vitronectin, kininogen
Abstract: The urokinase receptor (uPAR) is an important part of the plasminogen activation system. Urokinase-type plasminogen activator (uPA) was the first identified ligand of uPAR. Therefore, the major role of uPAR was thought to be in the regulation of pericellular proteolysis through the activation of plasminogen into active plasmin. However, recent studies have shown that uPA binding to uPAR plays a pivotal role in signaling functions that influence cell behaviour. Newly identified ligands, vitronectin and high molecular kinin-free kininogen, suggest tha t uPA R also has adhe sive and a nti-a dhesive pr operties. In a ddition, being a glycosyl-phospha tidylinositol (GPI)-anchored protein, uPAR can interact laterally with a wide variety of membrane proteins including integrins, endocytic receptors, caveolin, the gp130 cytokine receptor, the EGF receptor, and FPRL1 a classical chemoattractant receptor. These interactions underline the importance of uPAR, despite its lack of an intracellular domain, in many cell events including adhesion, migration, growth and gene expression. More importantly, the role of uPAR in adhesion, extravasation, chemotaxis of leukocytes, and tissue repair explains its involvement in the early and late events of the inflammatory reaction. Thus, emerges the concept that uPAR is at the centre of an integrative signaling network with proand anti-inflammatory attributes that may lead to the identification of new therapeutic targets. We propose to classify uPAR into a new group of membrane proteins having a chemokine-like function and to name this new class MACKINE (Membrane-Anchored ChemoKINE-like proteins).
