The urokinase receptor associated protein (uPARAP/endo180): a novel internalization receptor connected to the plasminogen activation system.
The urokinase-mediated plasminogen activation system plays a central role in the extracellular proteolytic degradation reactions in cancer invasion. In this review article we discuss a number of recent findings identifying a new cellular receptor protein, uPARAP, that interacts with components of this proteolytic system. uPARAP is a high molecular weight type-1 membrane protein, belonging to the macrophage mannose receptor protein family. On the surface of certain cells, uPARAP forms a ternary complex with the pro-form of the urokinase-type plasminogen activator (uPA) and its primary receptor (uPAR). While the biological consequences of this reaction have not yet been verified experimentally, a likely event is ligand internalization because uPARAP is a constitutively recycling internalization receptor. uPARAP also binds at least one component, collagen type V, in the extracellular matrix meshwork, pointing to a potential role in proteolytic substrate presentation. Additional ligands have been proposed, including collagenase-3 and glycoproteins capable of interacting with one of the multiple carbohydrate recognition-type domains of uPARAP. In various adult tissues uPARAP is present on fibroblasts, macrophages and a subset of endothelial cells. In fetal tissues the protein has also been demonstrated in certain bone forming regions. Hypotheses on the physiological function of uPARAP include regulatory roles in extracellular proteolysis. This type of function would be likely to direct the local turnover of proteases and their substrate degradation products and thus may add to the complicated interplay between several cell types in governing restricted tissue degradation.
Engelholm
L H
LH
The Finsen Laboratory, Rigshospitalet, Ø, Copenhagen, Denmark.
Nielsen
B S
BS
Danø
K
K
Behrendt
N
N
D000818:Animals; D006801:Humans; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D009369:Neoplasms / Q000378:metabolism; D010447:Peptide Hydrolases / Q000378:metabolism; D010960:Plasminogen Activators / Q000737:chemistry / Q000502:physiology*; D011485:Protein Binding; D011956:Receptors, Cell Surface / Q000032:analysis / Q000737:chemistry / Q000502:physiology*; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry / Q000502:physiology*
C404106:MRC2 protein, human; D037241:Mannose-Binding Lectins; D008562:Membrane Glycoproteins; C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D010447:Peptide Hydrolases; D010960:Plasminogen Activators; D014568:Urokinase-Type Plasminogen Activator