The urokinase receptor associated protein (uPARAP/Endo180): A novel internalization receptor connected to the plasminogen activation system

Citation
Lh. Engelholm et al., The urokinase receptor associated protein (uPARAP/Endo180): A novel internalization receptor connected to the plasminogen activation system, TREND CARD, 11(1), 2001, pp. 7-13
Citations number
61
Categorie Soggetti
Cardiovascular & Hematology Research
Journal title
TRENDS IN CARDIOVASCULAR MEDICINE
ISSN journal
10501738 → ACNP
Volume
11
Issue
1
Year of publication
2001
Pages
7 - 13
Database
ISI
SICI code
1050-1738(200101)11:1<7:TURAP(>2.0.ZU;2-#
Abstract
The urokinase-mediated plasminogen activation system plays a central role i n the extracellular proteolytic degradation reactions in cancer invasion. I n this review article we discuss a number of recent findings identifying a new cellular receptor protein uPARAP, that interacts with components of thi s cellular receptor protein, uPARAP is a high molecular weight type-1 membr ane protein ,belonging to the macrophage mannose receptor protein family. O N the surface of certain cells, uPARAP forms a ternary complex with the pro -form of the urokinase-type plasminogen activator (uPA) and its primary rec eptor (uPAR). While the biological consequences of this reaction have not y et been verified experimentally, a likely event is ligand internalization b ecause uPARAP is a constitutively recycling internalization receptor. uPARA P also binds at least one component, collagen type V, in the extracellular matrix meshwork, pointing to a potential role in proteolytic substrate pres entation. Additional ligands have been proposed, including collagenase-3 an d glycoproteins capable of interacting with one of the multiple carbohydrat e recognition-type domains of uPARAP. In various adult tissues uPARAP is pr esent on fibroblasts, macrophages and a subset of endothelial cells. In fet al tissues the protein has also been demonstrated in certain bone forming r egions. Hypotheses on the physiological function of uPARAP include regulato ry roles in extracellular proteolysis. This type of function would be likel y to direct the local turnover of proteases and their substrate degradation products and thus may add to the complicated interplay between several cel l types in governing restricted tissue degradation. (C) 2001, Elsevier Scie nce Inc.