Arfaptin 1 inhibits ADP‐ribosylation factor‐dependent matrix metalloproteinase‐9 secretion induced by phorbol ester in HT 1080 fibrosarcoma cells

FEBS Letters

Exton, John H.¹  Ho, Wan-Ting¹  Williger, Ben-Tsion² 

[1] Howard Hughes Medical Institute and Department of Molecular Physiology and Biophysics, Vanderbilt University School of Medicine, Nashville, TN 38232-0295, USA;CancerTek Pharmaceuticals Ltd., P.O. Box 3, Ariel 44837, Israel

关键词: ADP-ribosylation factor;    Arfaptin;    Phospholipase D;    Phosphatidic acid;    Matrix metalloproteinase;    ARF;    ADP-ribosylation factor;    BFA;    brefeldin A;    BSA;    bovine serum albumin;    DMEM;    Dulbecco's modified Eagle's medium;    ECL;    enhanced chemiluminescence;    FCS;    fetal calf serum;    GEF;    guanine nucleotide exchange factor;    MMP-9;    matrix metalloproteinase-9;    PA;    phosphatidic acid;    PBS;    phosphate-buffered saline;    PKC;    protein kinase C;    PLD;    phospholipase D;    PMA;    phorbol 12-myristate 13-acetate;    PtdBut;    phosphatidylbutanol;    SDS–PAGE;    sodium dodecyl sulfate–polyacrylamide gel electrophoresis;    VSV-G;    vesicular stomatitis virus glycoprotein;   

DOI  :  10.1016/S0014-5793(03)00098-X

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Matrix metalloproteinase-9 (MMP-9) is a collagenolytic enzyme secreted by cancer cells and involved in invasiveness and metastasis. Its secretion from human fibrosarcoma HT 1080 cells is markedly enhanced by phorbol 12-myristate 13-acetate (PMA) and abolished by brefeldin A, an inhibitor of ADP-ribosylation factor (ARF) activation. These results support a role for ARF in PMA-stimulated MMP-9 secretion. Overexpression of arfaptin 1, a 39 kDa ARF-binding protein that inhibits in vitro activation of cholera toxin ADP-ribosyltransferase and phospholipase D (PLD) by ARF, inhibited PMA-stimulated MMP-9 and PLD activation. These data are in agreement with previous results demonstrating a significant role for PLD in regulating MMP-9 secretion.

【 授权许可】

Unknown