PMID- 8999957
OWN - NLM
STAT- MEDLINE
DCOM- 19970221
LR  - 20210209
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 272
IP  - 4
DP  - 1997 Jan 24
TI  - Membrane type 1 matrix metalloproteinase digests interstitial collagens and other 
      extracellular matrix macromolecules.
PG  - 2446-51
AB  - Membrane type 1 matrix metalloproteinase (MT1-MMP) is expressed on cancer cell 
      membranes and activates the zymogen of MMP-2 (gelatinase A). We have recently 
      isolated MT1-MMP complexed with tissue inhibitor of metalloproteinases 2 (TIMP-2) 
      and demonstrated that MT1-MMP exhibits gelatinolytic activity by gelatin 
      zymography (Imai, K., Ohuchi, E., Aoki, T., Nomura, H., Fujii, Y., Sato, H., 
      Seiki, M., and Okada, Y. (1996) Cancer Res. 56, 2707-2710). In the present study, 
      we have further purified to homogeneity a deletion mutant of MT1-MMP lacking the 
      transmembrane domain (DeltaMT1) and native MT1-MMP secreted from a human breast 
      carcinoma cell line (MDA-MB-231 cells) and examined their substrate 
      specificities. Both proteinases are active, without any treatment for activation, 
      and digest type I (guinea pig), II (bovine), and III (human) collagens into 
      characteristic 3/4 and 1/4 fragments. The cleavage sites of type I collagen are 
      the Gly775-Ile776 bond for alpha1(I) chains and the Gly775-Leu776 and 
      Gly781-Ile782 bonds for alpha2(I) chains. DeltaMT1 hydrolyzes type I collagen 
      6.5- or 4-fold more preferentially than type II or III collagen, whereas MMP-1 
      (tissue collagenase) digests type III collagen more efficiently than the other 
      two collagens. Quantitative analyses of the activity of DeltaMT1 and MMP-1 
      indicate that DeltaMT1 is 5-7.1-fold less efficient at cleaving type I collagen. 
      On the other hand, gelatinolytic activity of DeltaMT1 is 8-fold higher than that 
      of MMP-1. DeltaMT1 also digests cartilage proteoglycan, fibronectin, vitronectin 
      and laminin-1 as well as alpha1-proteinase inhibitor and alpha2-macroglobulin. 
      The activity of DeltaMT1 on type I collagen is synergistically increased with 
      co-incubation with MMP-2. These results indicate that MT1-MMP is an extracellular 
      matrix-degrading enzyme sharing the substrate specificity with interstitial 
      collagenases, and suggest that MT1-MMP plays a dual role in pathophysiological 
      digestion of extracellular matrix through direct cleavage of the substrates and 
      activation of proMMP-2.
FAU - Ohuchi, E
AU  - Ohuchi E
AD  - Department of Molecular Immunology and Pathology, Cancer Research Institute, 
      Kanazawa University, 13-1 Takara-machi, Kanazawa, Ishikawa 920, Japan.
FAU - Imai, K
AU  - Imai K
FAU - Fujii, Y
AU  - Fujii Y
FAU - Sato, H
AU  - Sato H
FAU - Seiki, M
AU  - Seiki M
FAU - Okada, Y
AU  - Okada Y
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - United States
TA  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Fibronectins)
RN  - 0 (Glycoproteins)
RN  - 0 (Laminin)
RN  - 0 (Matrix Metalloproteinase Inhibitors)
RN  - 0 (Protease Inhibitors)
RN  - 0 (Proteins)
RN  - 0 (Tissue Inhibitor of Metalloproteinases)
RN  - 0 (Vitronectin)
RN  - 127497-59-0 (Tissue Inhibitor of Metalloproteinase-2)
RN  - 9000-70-8 (Gelatin)
RN  - 9007-34-5 (Collagen)
SB  - IM
MH  - Collagen/*metabolism
MH  - Electrophoresis, Polyacrylamide Gel
MH  - Extracellular Matrix/*metabolism
MH  - Fibronectins/metabolism
MH  - Gelatin/metabolism
MH  - Glycoproteins/*metabolism
MH  - Humans
MH  - Laminin/metabolism
MH  - *Matrix Metalloproteinase Inhibitors
MH  - Protease Inhibitors/*metabolism
MH  - Proteins/metabolism
MH  - Substrate Specificity
MH  - Tissue Inhibitor of Metalloproteinase-2
MH  - Tissue Inhibitor of Metalloproteinases
MH  - Vitronectin/metabolism
EDAT- 1997/01/24 00:00
MHDA- 1997/01/24 00:01
CRDT- 1997/01/24 00:00
PHST- 1997/01/24 00:00 [pubmed]
PHST- 1997/01/24 00:01 [medline]
PHST- 1997/01/24 00:00 [entrez]
AID - S0021-9258(19)78524-X [pii]
AID - 10.1074/jbc.272.4.2446 [doi]
PST - ppublish
SO  - J Biol Chem. 1997 Jan 24;272(4):2446-51. doi: 10.1074/jbc.272.4.2446.