Tissue inhibitor of metalloproteinase (TIMP)-2 acts synergistically with synthetic matrix metalloproteinase (MMP) inhibitors but not with TIMP-4 to enhance the (membrane type 1)-MMP-dependent activation of pro-MMP-2

Toth M, Bernardo MM, Gervasi DC, Soloway PD, Wang ZP, Bigg HF, Overall CM, DeClerck YA, Tschesche H, Cher ML, Brown S, et al. (2000)
JOURNAL OF BIOLOGICAL CHEMISTRY 275(52): 41415-41423.

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Zeitschriftenaufsatz | Veröffentlicht | Englisch
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Abstract / Bemerkung
The membrane-type 1 matrix metalloproteinase (MT1-MMP) has been shown to be a key enzyme in tumor angiogenesis and metastasis. MT1-MMP hydrolyzes a variety of extracellular matrix components and is a physiological activator of pro-MMP-2, another MMP involved in malignancy. Pro-MMP-2 activation by MT1-MMP involves the formation of an MT1-MMP tissue inhibitors of metalloproteinases 2 (TIMP-2) pro-MMP-2 complex on the cell surface that promotes the hydrolysis of pro-MMP-2 by a neighboring TIMP-2-free MT1-MMP. The MT1-MMP TIMP-2 complex also serves to reduce the intermolecular autocatalytic turnover of MT1-MMP, resulting in accumulation of active MT1-MMP (57 kDa) on the cell surface. Evidence shown here in Timp2-null cells demonstrates that pro-MMP-2 activation by MT1-MMP requires TIMP-2. In contrast, a C-terminally deleted TIMP-2 (Delta -TIMP-2), unable to form ternary complex, had no effect, However, Delta -TIMP-2 and certain synthetic MMP inhibitors, which inhibit MT1-MMP autocatalysis, can act synergistically with TIMP-2 in the promotion of pro-MMP-2 activation by MT1-MMP. In contrast, TIMP-4, an efficient MT1-MMP inhibitor, had no synergistic effect, These studies suggest that under certain conditions the pericellular activity of MT1-MMP in the presence of TIMP-2 can be modulated by synthetic and natural (TIMP-4) MMP inhibitors.
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Zeitschriftentitel
JOURNAL OF BIOLOGICAL CHEMISTRY
Band
275
Zeitschriftennummer
52
Seite
41415-41423
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Toth M, Bernardo MM, Gervasi DC, et al. Tissue inhibitor of metalloproteinase (TIMP)-2 acts synergistically with synthetic matrix metalloproteinase (MMP) inhibitors but not with TIMP-4 to enhance the (membrane type 1)-MMP-dependent activation of pro-MMP-2. JOURNAL OF BIOLOGICAL CHEMISTRY. 2000;275(52):41415-41423.
Toth, M., Bernardo, M. M., Gervasi, D. C., Soloway, P. D., Wang, Z. P., Bigg, H. F., Overall, C. M., et al. (2000). Tissue inhibitor of metalloproteinase (TIMP)-2 acts synergistically with synthetic matrix metalloproteinase (MMP) inhibitors but not with TIMP-4 to enhance the (membrane type 1)-MMP-dependent activation of pro-MMP-2. JOURNAL OF BIOLOGICAL CHEMISTRY, 275(52), 41415-41423. doi:10.1074/jbc.M006871200
Toth, M., Bernardo, M. M., Gervasi, D. C., Soloway, P. D., Wang, Z. P., Bigg, H. F., Overall, C. M., DeClerck, Y. A., Tschesche, H., Cher, M. L., et al. (2000). Tissue inhibitor of metalloproteinase (TIMP)-2 acts synergistically with synthetic matrix metalloproteinase (MMP) inhibitors but not with TIMP-4 to enhance the (membrane type 1)-MMP-dependent activation of pro-MMP-2. JOURNAL OF BIOLOGICAL CHEMISTRY 275, 41415-41423.
Toth, M., et al., 2000. Tissue inhibitor of metalloproteinase (TIMP)-2 acts synergistically with synthetic matrix metalloproteinase (MMP) inhibitors but not with TIMP-4 to enhance the (membrane type 1)-MMP-dependent activation of pro-MMP-2. JOURNAL OF BIOLOGICAL CHEMISTRY, 275(52), p 41415-41423.
M. Toth, et al., “Tissue inhibitor of metalloproteinase (TIMP)-2 acts synergistically with synthetic matrix metalloproteinase (MMP) inhibitors but not with TIMP-4 to enhance the (membrane type 1)-MMP-dependent activation of pro-MMP-2”, JOURNAL OF BIOLOGICAL CHEMISTRY, vol. 275, 2000, pp. 41415-41423.
Toth, M., Bernardo, M.M., Gervasi, D.C., Soloway, P.D., Wang, Z.P., Bigg, H.F., Overall, C.M., DeClerck, Y.A., Tschesche, H., Cher, M.L., Brown, S., Mobashery, S., Fridman, R.: Tissue inhibitor of metalloproteinase (TIMP)-2 acts synergistically with synthetic matrix metalloproteinase (MMP) inhibitors but not with TIMP-4 to enhance the (membrane type 1)-MMP-dependent activation of pro-MMP-2. JOURNAL OF BIOLOGICAL CHEMISTRY. 275, 41415-41423 (2000).
Toth, M, Bernardo, MM, Gervasi, DC, Soloway, PD, Wang, ZP, Bigg, HF, Overall, CM, DeClerck, YA, Tschesche, Harald, Cher, ML, Brown, S, Mobashery, S, and Fridman, R. “Tissue inhibitor of metalloproteinase (TIMP)-2 acts synergistically with synthetic matrix metalloproteinase (MMP) inhibitors but not with TIMP-4 to enhance the (membrane type 1)-MMP-dependent activation of pro-MMP-2”. JOURNAL OF BIOLOGICAL CHEMISTRY 275.52 (2000): 41415-41423.

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Daten bereitgestellt von Europe PubMed Central.

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