PMID- 7890645
OWN - NLM
STAT- MEDLINE
DCOM- 19950414
LR  - 20231120
IS  - 0021-9258 (Print)
IS  - 0021-9258 (Linking)
VI  - 270
IP  - 10
DP  - 1995 Mar 10
TI  - Mechanism of cell surface activation of 72-kDa type IV collagenase. Isolation of 
      the activated form of the membrane metalloprotease.
PG  - 5331-8
AB  - Matrix metalloproteases are secreted by mammalian cells as zymogens and, upon 
      activation, initiate tissue remodeling by proteolytic degradation of collagens 
      and proteoglycans. Activation of the secreted proenzymes and interaction with 
      their specific inhibitors determine the net enzymatic activity in the 
      extracellular space. We have previously demonstrated that 72T4Cl can be activated 
      by a plasma membrane-dependent mechanism specific for this enzyme. Here, we 
      report purification of the membrane activator of 72T4Cl, which is a new 
      metalloprotease identical to a recently cloned membrane-type matrix 
      metalloprotease (MT-MMP). We demonstrate that activated MT-MMP acts as a cell 
      surface tissue inhibitor of metalloprotease 2 (TIMP-2) receptor with Kd = 2.54 x 
      10(-9) M. The activator.TIMP-2 complex in turn acts as a receptor for 72T4Cl (Kd 
      = 0.56 x 10(-9) M, binding to the carboxyl-end domain of the enzyme. Activation 
      of 72T4Cl on the cell membrane provides a basic mechanism for spatially regulated 
      extracellular proteolysis and presents a new target for prognosis and treatment 
      of metastatic disease. The activation, purified as a tri-molecular complex of 
      MT-MMP.TIMP2.carboxyl-end domain of 72T4Cl, is itself an activated form of 
      MT-MMP, posing the following question: what is the mechanism of the activator's 
      activation?
FAU - Strongin, A Y
AU  - Strongin AY
AD  - Division of Dermatology, Washington University School of Medicine, St. Louis, 
      Missouri 63110-1093.
FAU - Collier, I
AU  - Collier I
FAU - Bannikov, G
AU  - Bannikov G
FAU - Marmer, B L
AU  - Marmer BL
FAU - Grant, G A
AU  - Grant GA
FAU - Goldberg, G I
AU  - Goldberg GI
LA  - eng
GR  - R01 AR39472/AR/NIAMS NIH HHS/United States
GR  - R01 AR40618/AR/NIAMS NIH HHS/United States
GR  - T32 AR07284/AR/NIAMS NIH HHS/United States
PT  - Comparative Study
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  - J Biol Chem
JT  - The Journal of biological chemistry
JID - 2985121R
RN  - 0 (Enzyme Precursors)
RN  - 0 (Recombinant Fusion Proteins)
RN  - 0 (Recombinant Proteins)
RN  - EC 3.4.24.- (Collagenases)
RN  - EC 3.4.24.- (Matrix Metalloproteinases, Membrane-Associated)
RN  - EC 3.4.24.- (Metalloendopeptidases)
RN  - EC 3.4.24.- (procollagenase)
SB  - IM
MH  - Amino Acid Sequence
MH  - Animals
MH  - Cell Line
MH  - Cell Membrane/*enzymology
MH  - Chromatography, Affinity
MH  - Cloning, Molecular
MH  - Collagenases/isolation & purification/*metabolism
MH  - Enzyme Activation
MH  - Enzyme Precursors/isolation & purification/*metabolism
MH  - Fibrosarcoma
MH  - Gene Library
MH  - Humans
MH  - Kinetics
MH  - Matrix Metalloproteinases, Membrane-Associated
MH  - Metalloendopeptidases/biosynthesis/*isolation & purification/*metabolism
MH  - Models, Theoretical
MH  - Molecular Sequence Data
MH  - Polymerase Chain Reaction
MH  - Recombinant Fusion Proteins/biosynthesis/isolation & purification
MH  - Recombinant Proteins/biosynthesis/isolation & purification/metabolism
MH  - Sequence Homology, Amino Acid
MH  - Skin/enzymology
MH  - Transfection
MH  - Tumor Cells, Cultured
EDAT- 1995/03/10 00:00
MHDA- 2000/03/23 09:00
CRDT- 1995/03/10 00:00
PHST- 1995/03/10 00:00 [pubmed]
PHST- 2000/03/23 09:00 [medline]
PHST- 1995/03/10 00:00 [entrez]
AID - S0021-9258(18)94757-5 [pii]
AID - 10.1074/jbc.270.10.5331 [doi]
PST - ppublish
SO  - J Biol Chem. 1995 Mar 10;270(10):5331-8. doi: 10.1074/jbc.270.10.5331.