PMID- 2176865
OWN - NLM
STAT- MEDLINE
DCOM- 19910227
LR  - 20190613
IS  - 0006-2960 (Print)
IS  - 0006-2960 (Linking)
VI  - 29
IP  - 44
DP  - 1990 Nov 6
TI  - Mechanisms of activation of tissue procollagenase by matrix metalloproteinase 3 
      (stromelysin).
PG  - 10261-70
AB  - The mechanism of activation of tissue procollagenase by matrix metalloproteinase 
      3 (MMP-3)/stromelysin was investigated by kinetic and sequence analyses. MMP-3 
      slowly activated procollagenase by cleavage of the Gln80-Phe81 bond to generate a 
      fully active collagenase of Mr = 41,000. The specific collagenolytic activity of 
      this species was 27,000 units/mg (1 unit = 1 microgram of collagen digested in 1 
      min at 37 degrees C). Treatment of procollagenase with plasmin or plasma 
      kallikrein gave intermediates of Mr = 46,000. These intermediates underwent rapid 
      autolytic activation, via cleaving the Thr64-Leu65 bond, to give a collagenase 
      species of Mr = 43,000 that exhibited only about 15% of the maximal specific 
      activity. Similarly, (4-aminophenyl)mercuric acetate (APMA) activated 
      procollagenase by intramolecular cleavage of the Val67-Met68 bond to generate a 
      collagenase species of Mr = 43,000, but with only about 25% of the maximal 
      specific activity. Subsequent incubation of the 43,000-Mr species with MMP-3 
      resulted in rapid, full activation and generated the 41,000-Mr collagenase by 
      cleaving the Gln80-Phe81 bond. In the case of the proteinase-generated 43,000-Mr 
      species, the action of MMP-3 was approximately 24,000 times faster than that on 
      the native procollagenase. This indicates that the removal of a portion of the 
      propeptide of procollagenase induces conformational changes around the 
      Gln80-Phe81 bond, rendering it readily susceptible to MMP-3 activation. Prolonged 
      treatment of procollagenase with APMA in the absence of MMP-3 also generated a 
      41,000-Mr collagenase, but this species had only 40% of the full activity and 
      contained Val82 and Leu83 as NH2 termini. Thus, cleavage of the Gln80-Phe81 bond 
      by MMP-3 is crucial for the expression of full collagenase activity. These 
      results suggest that the activation of procollagenase by MMP-3 is regulated by 
      two pathways: one with direct, slow activation by MMP-3 and the other with rapid 
      activation in conjunction with tissue and/or plasma proteinases. The latter event 
      may explain an accelerated degradation of collagens under certain physiological 
      and pathological conditions.
FAU - Suzuki, K
AU  - Suzuki K
AD  - Department of Biochemistry and Molecular Biology, University of Kansas Medical 
      Center, Kansas City 66103.
FAU - Enghild, J J
AU  - Enghild JJ
FAU - Morodomi, T
AU  - Morodomi T
FAU - Salvesen, G
AU  - Salvesen G
FAU - Nagase, H
AU  - Nagase H
LA  - eng
GR  - AR 39189/AR/NIAMS NIH HHS/United States
GR  - CA 29589/CA/NCI NIH HHS/United States
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PT  - Research Support, U.S. Gov't, P.H.S.
PL  - United States
TA  - Biochemistry
JT  - Biochemistry
JID - 0370623
RN  - 0 (Enzyme Precursors)
RN  - EC 3.4.24.- (Collagenases)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.- (procollagenase)
RN  - EC 3.4.24.17 (Matrix Metalloproteinase 3)
RN  - EC 3.4.24.3 (Microbial Collagenase)
SB  - IM
MH  - Amino Acid Sequence
MH  - *Collagenases
MH  - Enzyme Activation
MH  - Enzyme Precursors/*metabolism
MH  - Matrix Metalloproteinase 3
MH  - Metalloendopeptidases/*metabolism
MH  - Microbial Collagenase/*metabolism
MH  - Molecular Sequence Data
EDAT- 1990/11/06 00:00
MHDA- 1990/11/06 00:01
CRDT- 1990/11/06 00:00
PHST- 1990/11/06 00:00 [pubmed]
PHST- 1990/11/06 00:01 [medline]
PHST- 1990/11/06 00:00 [entrez]
AID - 10.1021/bi00496a016 [doi]
PST - ppublish
SO  - Biochemistry. 1990 Nov 6;29(44):10261-70. doi: 10.1021/bi00496a016.