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Keywords:

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

Abstract

  1. Top of page
  2. Abstract
  3. References

Human progelatinase B was activated by collagenase-3 in a time-dependent fashion. Activation proceeded through an intermediate form of Mr 86000 to the final active form of Mr 82000. 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.

Abbreviations.
MMP

matrix metalloproteinase

TIMP

tissue inhibitor of metalloproteinase

MT1-MMP

membrane-type matrix metalloproteinase

MMP-9

gelatinase B

MMP-13

collagenase-3

AcHgPhNH2

aminophenyl mercuric acetate

McaPLGLDnp(NH2)2PrARNH2

(7-meth-oxycoumarin-4-yl)acetyl-Pro-Leu-Gly-Leu-[3-(2,4-dinitrophenyl)-L-2, 3-diaminopropyl]Ala-Arg-NH2

 

chromatography

uPA

urokinase-like plasminogen activator

uPAR

urokinase-plasminogen-activator receptor

References

  1. Top of page
  2. Abstract
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