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...ed for ability to bind andsstabilize PAI-1.sResults reported that all 8 cysteines and Gly12, Asp22, Leu24, Tyr27,sTyr28, and Asp34 were necessary to preserve PAI-1 activity.sAdditionally, Deng et al. =-=(53)-=- demonstrated that mAB 153 inhibited the bindingsof plasminogen activator and urokinase plasminogen activator receptor (uPAR) tosvitronectin, thus also suggesting the binding sites for these ligands i...

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...g the rapid endocytosis of the trimolecular uPA–PAI-1–uPAR complex (Conese and Blasi, 1995; Blasi, 1997). However, it has also been implicated in modulating cell migration via alternative mechanisms (=-=Deng et al., 1996-=-; Stefansson and Lawrence, 1996; Blasi, 1997; Loskutoff et al., 1999), even though conclusive in vivo evidence is lacking. By blocking the interaction between vitronectin (VN), uPAR, and integrins, PA...

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...a is 400 pM (Rijken & Lijnen, 2009). In addition tosfibrinolysis, PAI-1 regulates cell migration by modulating ECM, regulating cell adhesion,sand modifying the formation of chemoattractant gradients (=-=Deng et al., 1996-=-; Czekay et al.,s2003; Marshall et al., 2003). PAI-1 levels are increased in patients with gastric cancer, severespneumonia, or sepsis (Pralong et al., 1989; Günther et al., 2000; Kaneko et al., 2003;...

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...B activation and increases RhoB expression.suPAR expression regulates PC3 cell adhesion to vitronectinsuPAR mediates adhesion of a variety of cell types to VN, since it is a non-integrin VN receptors(=-=Deng et al., 1996-=-; Wei et al., 1996; Madsen and Sidenius, 2008; Blasi and Sidenius, 2010).sConsistent with this, uPAR overexpression in PC3 cells increased cell elongation and spread areas(Fig. 6A), and increased thei...

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... and Worrall, 2002). We believe that maspin is likely to interact with multiple target molecules, such as its homologue PAI-1 that also functions through interactions with several different proteins (=-=Deng et al., 1996-=-; Stefansson et al., 1996). Over the last few years, we have focused our efforts to characterize the role of maspin in breast tumor progression, demonstrating that maspin is indeed capable of inhibiti...

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...activation and increases RhoB expression. uPAR expression regulates PC3 cell adhesion to vitronectin uPAR mediates adhesion of a variety of cell types to VN, because it is a non-integrin VN receptor (=-=Deng et al., 1996-=-; Wei et al., 1996; Madsen and Sidenius, 2008; Blasi and Sidenius, 2010). Consistent with this, uPAR overexpression in PC3 cells increased cell elongation and spread area (Fig. 6A), and increased thei...

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...behaves as a proteolysis-dependent agonist of uPAR-mediated cell adhesion on VN A prediction of the above findings is that specific inhibitors of uPA and Pli may stabilize cell adhesion in conditions where the plasminogen activation system is active. In particular, PAI-1 is expected to be of central importance in this respect as it is both an irreversible inhibitor of uPA as well as a potent competitive antagonist of the uPAR/VN interaction. Complex formation between uPA and PAI-1 results in the loss of two activities that suppress cell adhesion, that is the competitive binding of PAI-1 to VN [26] and the A B C D E F Figure 4. The cleavage of VN by tc-uPA requires the binding of both uPA and VN to uPAR. A Plasminogen activation results in the generation of N-terminal VN fragments containing the SMB domain. 293/uPAR cells were seeded on VN and treated with 10 nM sc-uPA and tc-uPA, 30 nM Plg and Pli, and 100 nM a2AP for 2 h at 37°C. The supernatants were harvested and the level of SMB-containing VN fragments was measured by immunoassay (see Materials and Methods section). Values represent the mean SD of at least 3 independent experiments. The statistical significance was probed using S...

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...f VN (Okumura et al., 2002) and are immediately adjacent to the single RGD sequence in the molecule. The affinity of PAI-1 for the SMB domain is much higher than the affinity of uPAR for this domain (=-=Deng et al., 1996-=-). Thus, PAI-1 can competitively inhibit the uPAR-dependent attachment of cells to VN (Deng et al., 1996; Waltz et al., 1997; Deng et al., 2001). Binding of PAI-1 to SMB also inhibits integrin-mediate...