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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
Author(s) -
Dear Anthony E,
Costa Magdaline,
Medcalf Robert L
Publication year - 1997
Publication title -
febs letters
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.593
H-Index - 257
eISSN - 1873-3468
pISSN - 0014-5793
DOI - 10.1016/s0014-5793(97)00002-1
Subject(s) - transactivation , microbiology and biotechnology , plasminogen activator , activator (genetics) , urokinase receptor , gene expression , transfection , signal transduction , biology , transcription factor , phorbol , regulation of gene expression , urokinase , chemistry , gene , protein kinase c , biochemistry , endocrinology , genetics
Urokinase‐type plasminogen activator (u‐PA) bound to its receptor, u‐PAR, initiates signal transduction pathways able to induce expression of the activator protein‐1 (AP‐1) family member c‐fos [1]. Since transcription factors bound to AP‐1 recognition sequences within the PAI‐2 gene promoter play a role in basal and phorbol ester‐mediated induction of PAI‐2 gene expression, we hypothesised that u‐PA/u‐PAR‐mediated modulation of AP‐1 activity would in turn influence constitutive and inducible PAI‐2 gene expression. Treatment of HT‐1080 or U‐937 cells with high molecular weight u‐PA (HMW u‐PA) resulted in induction of nuclear proteins binding to a functional AP‐1 element in the proximal PAI‐2 promoter. This increase in AP‐1 activity correlated with a transactivation of the PAI‐2 gene promoter in transiently transfected HT‐1080 cells. We also demonstrate the u‐PA treatment potentiated phorbol ester (PMA)‐mediated induction of PAI‐2 mRNA, indicating that u‐PA binding produces a bone fide response in vivo.