ADAM10 activity is more strongly inhibited by EDTA than ADAM17. (A,B) After 6 h of starvation in Opti-MEM, WT mEFs were treated with 4-amino-phenylmercuric acetate (APMA, 200 µM) in the presence or absence of 5 mM of EDTA for 30 min. APMA treatment induced the shedding of the ADAM17 substrate TGFα-AP (A) and the ADAM10 substrate BTC-AP (B). APMA-induced BTC-AP shedding, which depends on ADAM10, was more strongly reduced by treatment with 5 mM of EDTA than APMA-induced TGFα-AP shedding, which depends on ADAM17. In addition, PMA-induced TGFα-AP shedding, which depends on ADAM17, was not significantly reduced in the presence of EDTA (C). Data are shown as mean ± SEM for n ≥ 3 independent experiments. * indicates p < 0.05 and n.s. indicates no statistically significant difference using one-way ANOVA followed by Tukey’s multiple comparisons test.