Structure-function relationships in the interaction between the urokinase-type plasminogen activator and its receptor.
Degradation of the extracellular matrix plays an important role in a number of normal and pathological conditions involving active tissue remodeling such as postlactational mammary gland involution, wound healing and tumor invasion and metastasis. The expression of a high-affinity, glycolipid-anchored receptor for the urokinase-type plasminogen activator (uPAR) is often up-regulated during such tissue remodeling events. uPAR may, therefore, in cooperation with various matrix metalloproteases, serve to facilitate the proteolytic breakdown of the extracellular matrix via uPA catalyzed plasminogen activation at the foci where cellular invasion occurs. Consistent with such a role for uPAR in pericellular proteolysis is the observation that the membrane assembly of both plasminogen, via its lysine binding-sites, and of pro-uPA, via its tight binding to uPAR, is required to favor and confine plasminogen activation potential in proximity of the cell surface. This review will focus on molecular properties of uPAR including its membrane attachment by glycosyl-phosphatidylinositol, its multidomain structure and its relationship to the Ly-6/uPAR/alpha-neurotoxin protein domain family. Furthermore a mapping of the functional epitopes for uPA binding as well as a competitive peptide antagonist of the uPA-uPAR interaction will be discussed.
Ploug
Michael
M
Finsen Laboratory, Rigshospitalet, Strandboulevarden 49, DK-2100 Copenhagen Ø, Denmark. m-ploug@finsenlab.dk
D000595:Amino Acid Sequence; D000818:Animals; D006801:Humans; D008969:Molecular Sequence Data; D011956:Receptors, Cell Surface / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*; D055293:Receptors, Urokinase Plasminogen Activator; D020539:Sequence Analysis, Protein / Q000379:methods; D017386:Sequence Homology, Amino Acid; D013329:Structure-Activity Relationship; D014568:Urokinase-Type Plasminogen Activator / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
C524898:PLAUR protein, human; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D014568:Urokinase-Type Plasminogen Activator