The urokinase receptor (uPAR) and the uPAR-associated protein (uPARAP/ Endo180): membrane proteins engaged in matrix turnover during tissue remodeling

Abstract

The breakdown of the barriers formed by extracellular matrix proteins is a pre-requisite for all processes of tissue remodeling. Matrix degradation reactions take part in specific physiological events in the healthy organism but also represent a crucial step in cancer invasion. These degradation processes involve a highly organized interplay between proteases and their cellular binding sites as well as specific substrates and internalization receptors. This review article is focused on two components, the urokinase plasminogen activator receptor (uPAR) and the uPAR-associated protein (uPARAP, also designated Endo180), that are considered crucially engaged in matrix degradation. uPAR and uPARAP have highly diverse functions, but on certain cell types they interact with each other in a process that is still incompletely understood. uPAR is a glycosyl-phosphatidylinositol-anchored glycoprotein on the surface of various cell types that serves to bind the urokinase plasminogen activator and localize the activation reactions in the proteolytic cascade system of plasminogen activation. uPARAP is an integral membrane protein with a pronounced role in the internalization of collagen for intracellular degradation. Both receptors have additional functions that are currently being unraveled. The present discussion of uPAR and uPARAP is centered on their protein structure and molecular and cellular function.

Urokinase and its receptors in chronic kidney disease

“…PAI-1 and uPA are subsequently degraded within lysosomes while uPAR is recycled to the cell surface. The uPAR-associated protein (uPARAP/Endo180) is another internalization receptor connected with cell surface uPAR, that engages in matrix turnover during tissue remodeling (89,90).…”

Eight mutations including 5 novel ones in the COL1A1 gene in Czech patients with osteogenesis imperfecta

“…it may also play a role in the catabolism of extracellular matrix collagens. Finally, it is suggested this protein may participate in cell-matrix adhesion and cell migration 18,28 . The identified mutation disrupts the binding sequence.…”

Survey of the year 2004 commercial optical biosensor literature

“…cell adhesion [64], innate immunity [3], CO 2 assimilation in metabolic pathways [30], extracellular matrix degradation [2] and membrane construction [17,44,85]) as well as the binding properties of retrocyclins [14], apotosis regulators [42], antimicrobial peptides [23], glycosphingolipids [97], barley -amylase/subtilisin inhibitor [66], amelogenin [67], lysenin [45], lectins [65], endoxylases [40], connexins [21], selectins [25], phosphoinositides [71], carbohydrates [20,70,72], HIV proteins [48,91], tumor necrosis factor receptor superfamily [95] and the insulin-like growth factor system [58]. Other reviews highlight the integration of optical biosensors with complementary technologies in areas of applied research, including drug development and chemical genetics [1,50,73,83,88], plant proteomics [33], gene and protein expression [29,35,86], antibody optimization [5,46,62], food industry [4,47,54,61,79], bioprocessing and manufacturing [12,…”

“…We used three criteria to determine which technologies should be included in this survey: biosensor instruments must be (1) based on an optical detection method, either surface plasmon resonance or evanescent wave spectroscopy, (2) sold by a for-profit manufacturer or vendor and (3) able to monitor interaction kinetics. Based on these criteria, we found 928 primary research articles describing biosensor-based experiments performed using instruments produced by 13 manufacturers.…”