Academic Journal

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

التفاصيل البيبلوغرافية
العنوان: 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
المؤلفون: Toth, M, Bernardo, MM, Gervasi, DC, Soloway, PD, Wang, ZP, Bigg, HF, Overall, CM, DeClerck, YA, Tschesche, Harald, Cher, ML, Brown, S, Mobashery, S, Fridman, R
بيانات النشر: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC
سنة النشر: 2000
المجموعة: PUB - Publications at Bielefeld University
الوصف: 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. ; 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.
نوع الوثيقة: article in journal/newspaper
اللغة: English
Relation: info:eu-repo/semantics/altIdentifier/issn/0021-9258; info:eu-repo/semantics/altIdentifier/issn/1083-351X; info:eu-repo/semantics/altIdentifier/wos/000166114600099; info:eu-repo/semantics/altIdentifier/pmid/10998420; https://pub.uni-bielefeld.de/record/1618259
الاتاحة: https://pub.uni-bielefeld.de/record/1618259
Rights: info:eu-repo/semantics/closedAccess
رقم الانضمام: edsbas.7F074946
قاعدة البيانات: BASE