Urokinase‐mediated transactivation of the plasminogen activator inhibitor type 2 (PAI‐2) gene promoter in HT‐1080 cells utilises AP‐1 binding sites and potentiates phorbol ester‐mediated induction of endogenous PAI‐2 mRNA

Regulation of the plasminogen activator inhibitor-2 (PAI-2) gene in murine macrophages. Demonstration of a novel pattern of responsiveness to bacterial endotoxin

“…As an individual macrophage is attracted to a focus of LPS production, it may initially produce uPA and other mediators of extracellular proteolysis in order to penetrate the site and subsequently PAI-2 as part of the pro-coagulation cascade that is a feature of LPS-induced pathology. Consistent with this concept are recent data that indicate binding of uPA to its receptor induces expression of PAI-2 [39].…”

Plasminogen activator inhibitor type 2: a regulator of monocyte proliferation and differentiation

“…It is interesting that addition of u-PA to HT-1080 cells has also been shown to increase the expression of the endogenous PAI-2 gene. 43,44 When considering the results of this present study, we speculated that u-PA-mediated induction of PAI-2 may provide an autocrinenegative feedback loop designed to attenuate proliferative signals transmitted by the u-PA/uPAR complex.…”

The plasminogen activator system: biology and regulation

“…It seems that c-Jun and JunD are the major components binding to the AP1a element under both basal and PMA-treated conditions [151]. Basal and PMA-induced transcription of the PAI-2 gene promoter in HT1080 and U937 cells was significantly greater with a − 219-bp than with a − 1100-bp promoter construct, suggesting the presence of a repressor site between − 219 and − 1100 [151]. The PAI-2 gene is the most TNF-h responsive gene identified so far in several cell types.…”

“…Besides protein kinases, some transcription factors are upregulated or activated after uPA treatment. These include AP1 in HT1080 cells [151], as well as c-Jun and c-Myc in SAOS2 cells [152]. Thus, uPA induces uPAR-mediated activation of various kinases and transcription factors, and this may influence cytoskeletal structure, cell morphology, cell adhesion, and cell motility and migration.…”