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

FEBS Letters

Medcalf, Robert L¹  Costa, Magdaline¹  Dear, Anthony E¹ 

[1] Department of Medicine, Monash University, Box Hill Hospital, Box Hill, 3128 Victoria, Australia

关键词: Urokinase-type plasminogen activator;    Urokinase-type plasminogen receptor;    Signal transduction;    Activator protein-1;    PAI-2;    Gene expression;   

DOI  :  10.1016/S0014-5793(97)00002-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

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.

【 授权许可】

Unknown