Activation of ADAM 12 protease by copper

Conversion of latent proteases to the active form occurs by various mechani sms characteristic for different protease families. Here we report that the disintegrin metalloprotease ADAM 12-S is activated by Cu(II). Copper activ ation is distinct from the cysteine switch component of latency: eliminatio n of the ADAM 12 cysteine switch by a point mutation in the propeptide had no effect on copper activation, whereas mutation of an unpaired cysteine re sidue in the catalytic domain resulted in a mutant form of ADAM 12-S that w as insensitive to copper. This suggests a multi-step activation mechanism f or ADAM 12 involving both furin cleavage and copper binding. (C) 2001 Feder ation of European Biochemical Societies. Published by Elsevier Science B.V. All rights reserved.