title: Activation of ADAM 12 protease by copper.
abstract: Conversion of latent proteases to the active form occurs by various mechanisms characteristic for different protease families. Here we report that the disintegrin metalloprotease ADAM 12-S is activated by Cu(II). Copper activation is distinct from the cysteine switch component of latency: elimination 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 residue in the catalytic domain resulted in a mutant form of ADAM 12-S that was insensitive to copper. This suggests a multi-step activation mechanism for ADAM 12 involving both furin cleavage and copper binding.
authors.affiliation: Institute of Molecular Pathology, University of Copenhagen, Frederik V's Vej 11, DK-2100 Copenhagen, Denmark.
authors.forename: F
authors.initials: F
authors.lastname: Loechel
authors.forename: U M
authors.initials: UM
authors.lastname: Wewer
mesh_terms: D051722:ADAM Proteins; D000072199:ADAM12 Protein; D000510:Alpha-Globulins / Q000378:metabolism; D015153:Blotting, Western; D002850:Chromatography, Gel; D003300:Copper / Q000494:pharmacology*; D004789:Enzyme Activation; D006801:Humans; D008565:Membrane Proteins / Q000378:metabolism*; D008666:Metalloendopeptidases / Q000378:metabolism*; D011994:Recombinant Proteins / Q000378:metabolism
chemical_list: D000510:Alpha-Globulins; D008565:Membrane Proteins; D011994:Recombinant Proteins; C025500:alpha(2)-microglobulin; D003300:Copper; D051722:ADAM Proteins; D000072199:ADAM12 Protein; C000606480:ADAM12 protein, human; D008666:Metalloendopeptidases