Versican V1 proteolysis in human aorta in vivo occurs at the Glu(441)-Ala(442) bond, a site that is cleaved by recombinant ADAMTS-1 and ADAMTS-4

Mature human aorta contains a 70-kDa versican fragment, which reacts with a neoepitope antiserum to the C-terminal peptide sequence DPEAAE. This prote in therefore appears to represent the G1 domain of versican V1 (G1-DPEAAE(4 41)), which has been generated in vivo by proteolytic cleavage at the Glu(4 41)-Ala(442) bond, within the sequence DPEAAE(441)-A(442)RRGQ. Because the equivalent aggrecan product (G1-NITEGE(341)) and brevican product (GI-EAVES E(395)) are generated by ADAMTS-mediated cleavage of the respective proteog lycans, we tested the capacity of recombinant ADAMTS-1 and ADAMTS-4 to clea ve versican at Glu(441)-Ala(442). Both enzymes cleaved a recombinant versic an substrate and native human versican at the Glu(441)-Ala(442) bond and th e mature form of ADAMTS-4 was detected by Western analysis of extracts of a ortic intima. We conclude that versican V1 proteolysis in vivo can be catal yzed by one or more members of the ADAMTS family of metalloproteinases.