MEMBRANE-TYPE-1 MMP (MMP-14) CLEAVES AT 3 SITES IN THE AGGRECAN INTERGLOBULAR DOMAIN

An aggrecan G1-G2 substrate was used to determine sites within the int erglobular domain that were susceptible to cleavage by MT1-MMP. Degrad ation products were identified by Western blotting with neo-epitope an tibodies specific for MMP-derived N- and C-terminal sequences, The res ults showed that MT1-MMP cleaved at the N-341-F-342 and D-441-L-442 bo nds, as shown for other MMPs, and also at a site 13 amino acids C-term inal to the N-341-F-342 site. The G2 product of this additional cleava ge was identified by sequence analysis and revealed an N-terminus comm encing T(355)VxxPDVELPLP. The data are consistent with MT1-MMP cleavag e at three sites in the aggrecan interglobular domain; one at N-342-F- 342, a second at D-441-L-442 and a third at Q(354)-T-355. (C) 1998 Fed eration of European Biochemical Societies.