The urokinase receptor. A cell surface, regulated chemokine.
Mice deficient for the urokinase plasminogen activator (uPA) gene are deficient in the recruitment of T cells and macrophages and succumb to bacterial infections. High levels of uPA or of its receptor (uPAR, CD87) are produced in human cancers and are strong prognostic indicators of relapse. Thus uPA and uPAR have a profound influence on cell migration. This set of molecules is known to regulate surface proteolysis, cell adhesion and chemotaxis. We have investigated the mechanism involved in uPAR-dependent chemotaxis. Chemotaxis is induced through an uPA-dependent conformational change in uPAR which uncovers a very potent chemotactic epitope acting through a pertussis-toxin sensitive step and activating intracellular tyrosine kinases. The epitope is located in the linker region between domain D1 and D2 of uPAR. Binding of uPA transforms uPAR from a receptor for uPA into a pleiotropic ligand ("activated uPAR") for other still unidentified surface molecules. Through these "adaptors", uPAR causes cytoskeletal changes, activation of kinases and directional cell migration. The conformational change can be substituted by cleavage between domain D1 and D2, in an area that can be cleaved by uPA itself at high efficiency.
Blasi
F
F
Dipartimento di Ricerca Biologica e Tecnologica, H.S. Raffaele, Milano, Italy.
D000818:Animals; D002448:Cell Adhesion; D002465:Cell Movement; D002633:Chemotaxis; D006801:Humans; D009369:Neoplasms / Q000378:metabolism; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator
C524898:PLAUR protein, human; C524899:Plaur protein, mouse; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator