TIMP-2 is required for efficient activation of proMMP-2 in vivo.
Matrix metalloproteinases (MMPs) are synthesized as latent proenzymes. A proteolytic cleavage event involving processing of the cysteine-rich N-terminal propeptide is required for their full activation. Previous in vitro studies indicated that activation of proMMP-2 can occur through formation of a trimolecular complex between MMP-14, TIMP-2, and proMMP-2 at the cell surface. Using TIMP-2-deficient mice and cells derived from them, TIMP-2 was shown to be required for efficient proMMP-2 activation both in vivo and in vitro. The requirement for TIMP-2 was not cell-autonomous as exogenously added TIMP-2 could restore activation of proMMP-2 to TIMP-2-deficient cells. Mutant mice were overtly normal, viable, and fertile on the C57BL/6 background, indicating that both TIMP-2 and activated proMMP-2 are dispensable for normal development.
Wang
Z
Z
Roswell Park Cancer Institute, Department of Molecular and Cellular Biology, Buffalo, New York 16263, USA.
Juttermann
R
R
Soloway
P D
PD
D000818:Animals; D002417:Cattle; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D018093:Gelatinases / Q000378:metabolism*; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases / Q000378:metabolism*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D019715:Tissue Inhibitor of Metalloproteinase-1 / Q000378:metabolism; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000172:deficiency / Q000502:physiology*
D004792:Enzyme Precursors; D019715:Tissue Inhibitor of Metalloproteinase-1; D019716:Tissue Inhibitor of Metalloproteinase-2; D018093:Gelatinases; D053504:Matrix Metalloproteinases, Membrane-Associated; D008666:Metalloendopeptidases; C069860:progelatinase