Calcium influx inhibits MT1‐MMP processing and blocks MMP‐2 activation

FEBS Letters

Thompson, Erik W¹  Spiegel, Sarah²  Seiki, Motoharu³  Yu, Ming¹  Sato, Hiroshi⁴ 

[1] Department of Cell Biology, Georgetown University Medical Center, NW Washington, DC 20007, USA;Department of Biochemistry and Molecular Biology, Georgetown University Medical Center, NW Washington, DC 20007, USA;Department of Cancer Cell Research, Institute of Medical Science, University of Tokyo, 4-6-1 Shirogane dai, Minato-ku, Tokyo 108, Japan;Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Japan

关键词: Gelatinase A;    Activation;    Concanavalin A;    MT-MMP;    Calcium;    Human breast cancer;    Gel A;    gelatinase A;    ConA;    concanavalin A;    MMP-2;    matrix metalloproteinase-2;    MT1-MMP;    membrane type 1 matrix metalloproteinase;   

DOI  :  10.1016/S0014-5793(97)00849-1

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

We have previously reported that concanavalin A (ConA)-induced MMP-2 activation involves both transcriptional and non-transcriptional mechanisms. Here we examined the effects of calcium influx on MT1-MMP expression and MMP-2 activation in MDA-MB-231 cells. The calcium ionophore ionomycin caused a dose-dependent inhibition of ConA-induced MMP-2 activation, but had no effect on MT1-MMP mRNA levels. However, Western analysis revealed an accumulation of pro-MT1-MMP (63 kDa), indicating that ionomycin blocked the conversion of pro-MT1-MMP protein to the active 60 kDa form. This suggests that increased calcium levels inhibit the processing of MT1-MMP. This finding may help to elucidate the mechanism(s) which regulates MT1-MMP activation.

【 授权许可】

Unknown