Plasminogen activator inhibitor-1 regulates cell adhesion by binding to the somatomedin B domain of vitronectin.
Plasminogen activator inhibitor-1 (PAI-1) binds to the somatomedin B (SMB) domain of vitronectin. It inhibits the adhesion of U937 cells to vitronectin by competing with the urokinase receptor (uPAR; CD87) on these cells for binding to the same domain. Although the inhibitor also blocks integrin-mediated cell adhesion, the molecular basis of this effect is unclear. In this study, the effect of the inhibitor on the adhesion of a variety of cells (e.g., U937, MCF7, HT-1080, and HeLa) to vitronectin was assessed, and the importance of the SMB domain in these interactions was determined. Although PAI-1 blocked the adhesion of all of these cells to vitronectin-coated wells, it did not block adhesion to a variant of vitronectin which lacked the SMB domain. Interestingly, HT-1080 and U937 cells attached avidly to microtiter wells coated with purified recombinant SMB (which does not contain the RGD sequence), and this adhesion was again blocked by the inhibitor. These results affirm that PAI-1 can inhibit both uPAR- and integrin-mediated cell adhesion, and demonstrate that the SMB domain of vitronectin is required for these effects. They also show that multiple cell types can employ uPAR as an adhesion receptor. The use of purified recombinant SMB should help to further define this novel adhesive pathway, and to delineate its relationship with integrin-mediated adhesive events.
Deng
G
G
The Scripps Research Institute, Department of Vascular Biology, La Jolla, California 92037, USA.
Curriden
S A
SA
Hu
G
G
Czekay
R P
RP
Loskutoff
D J
DJ
D015703:Antigens, CD / Q000378:metabolism; D001665:Binding Sites; D002448:Cell Adhesion; D006367:HeLa Cells; D006801:Humans; D039564:Integrin alphaV; D008954:Models, Biological; D017395:Plasminogen Activator Inhibitor 1 / Q000378:metabolism* / Q000494:pharmacology*; D017434:Protein Structure, Tertiary; D011956:Receptors, Cell Surface / Q000378:metabolism; D055293:Receptors, Urokinase Plasminogen Activator; D017384:Sequence Deletion; D013002:Somatomedins / Q000378:metabolism; D014407:Tumor Cells, Cultured; D020298:U937 Cells; D019096:Vitronectin / Q000737:chemistry* / Q000235:genetics / Q000378:metabolism*
D015703:Antigens, CD; D039564:Integrin alphaV; C524898:PLAUR protein, human; D017395:Plasminogen Activator Inhibitor 1; D011956:Receptors, Cell Surface; D055293:Receptors, Urokinase Plasminogen Activator; D013002:Somatomedins; D019096:Vitronectin; C016756:somatomedin B