Calcium influx inhibits MT1-MMP processing and blocks MMP-2 activation.
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.
Yu
M
M
Department of Cell Biology, Georgetown University Medical Center, Washington, DC 20007, USA.
Sato
H
H
Seiki
M
M
Spiegel
S
S
Thompson
E W
EW
D015152:Blotting, Northern; D015153:Blotting, Western; D001943:Breast Neoplasms; D002118:Calcium / Q000378:metabolism* / Q000494:pharmacology*; D003208:Concanavalin A / Q000494:pharmacology; D004591:Electrophoresis, Polyacrylamide Gel; D004789:Enzyme Activation / Q000187:drug effects; D018093:Gelatinases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000378:metabolism*; D006801:Humans; D015759:Ionomycin / Q000494:pharmacology; D020778:Matrix Metalloproteinase 2; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000037:antagonists & inhibitors* / Q000096:biosynthesis / Q000187:drug effects / Q000378:metabolism*; D011499:Protein Processing, Post-Translational / Q000187:drug effects*; D014407:Tumor Cells, Cultured
D003208:Concanavalin A; D015759:Ionomycin; D018093:Gelatinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; D020778:Matrix Metalloproteinase 2; D002118:Calcium