Activation of progelatinase B (proMMP-9) by active collagenase-3 (MMP-13)

作者：Knauper V^*; Smith B; LopezOtin C; Murphy G

来源：European Journal of Biochemistry, 1997, 248(2): 369-373.

DOI：10.1111/j.1432-1033.1997.00369.x

• activation
• progelatinase B
• collagenase-3
• matrix metalloproteinases

Human progelatinase B was activated by collagenase-3 in a time-dependent fashion, Activation proceeded through an intermediate form of M-r 86 000 to the final active form of M-r 82 000. N-terminal amino acid sequence determination demonstrated that the Glu40-Met41 peptide bond was initially hydrolysed followed by cleavage of the Arg87-Phe88 peptide bond releasing the rest of the propeptide domain which was accompanied by the achievement of maximal enzymatic activity as revealed using a quenched fluorescent substrate. Kinetic analysis of activation revealed that the rates were dependent on the concentration of the proenzyme as well as active collagenase-3. Active gelatinase B did not contribute to the activation rate of the proenzyme initiated by collagenase-3 and our results indicate that progelatinase B activation proceeds via bimolecular cleavage with collagenase-3 involving sequential cleavage of the propeptide in two steps. The activation rates were not dependent on C-terminal domain interactions between progelatinase B and collagenase-3, as assessed using wild-type and C-terminal deletion mutants of both enzymes.
Since elevated levels of both gelatinase B and collagenase-3 have been observed in arthritis and breast cancer pathology these enzymes may well form a proteolytic cascade in these diseases which allows rapid turnover of the extracellular matrix.

• 出版日期1997-9-1