CLONING AND CHARACTERIZATION OF A NOVEL MATRIX METALLOPROTEINASE (MMP), CMMP, FROM CHICKEN-EMBRYO FIBROBLASTS - CMMP, XENOPUS XMMP, AND HUMAN MMP19 HAVE A CONSERVED UNIQUE CYSTEINE IN THE CATALYTIC DOMAIN

We cloned a novel matrix metalloproteinase (MMP) called CMMP from cult ured primary chicken embryo fibroblasts. The cDNA-derived CMMP sequenc e contains 472 amino acids including a putative 19-residue signal pept ide and a unique cysteine in the catalytic domain, an insertion in a s equence motif that binds the structural (noncatalytic) zinc of MMPs. S trikingly, a homologously inserted cysteine is also found in Xenopus X MMP and human MMP19, two recently cloned novel members of the MMP fami ly. Phylogenetic analysis suggest that XMMP and MMP19 represent foundi ng members of the MMP family, whereas CMMP is related to collagenase M MPs. Bacterially produced recombinant CMMP (without the amino-terminal inhibition domain), which was autoproteolyzed at the carboxyl-termina l domain, digested casein and gelatin. As shown by Northern blotting, CMMP mRNA of 1.8 kilobase pairs was constitutively expressed in cultur ed primary chicken embryo fibroblasts and up-regulated by tumor necros is factor-alpha and the phorbol ester 12-O-tetradecanoylphorbol-13-ace tate, but it was not regulated by interleukin-1, basic fibroblast grow th factor, or retinoic acid. CMMP mRNA of 1.8 kb was also detected in the head and body of 8-day-old chicken embryos and dramatically up-reg ulated in 9-day-old embryos.