Cellular activation of proMMP‐13 by MT1‐MMP depends on the C‐terminal domain of MMP‐13

FEBS Letters

Murphy, Gillian²  Soloway, Paul³  Patterson, Margaret L¹  Knäuper, Vera¹  Bailey, Louise¹  Worley, Joanna R¹ 

[1] School of Biological Sciences, University of East Anglia, Norwich NR4 7TJ, UK;University of Cambridge, Department of Oncology, Cambridge Institute for Medical Research, Hills Road, Cambridge CB2 2XY, UK;Roswell Park Cancer Institute, Department of Molecular and Cellular Biology, Buffalo, NY 16263, USA

关键词: Activation;    Procollagenase-3;    Membrane type matrix metalloproteinase 1;    TIMP-2 null mouse;    Progelatinase A;    Tissue inhibitor of metalloproteinase-2;    MMPs;    matrix metalloproteinases;    TIMPs;    tissue inhibitor of metalloproteinases;    proMMP-13;    procollagenase-3;    E205-A proMMP-13;    inactive point mutant of proMMP-13;    Δ249–451 proMMP-13;    C-terminal deletion mutant of MMP-13;    proMMP-13/19;    chimaeric MMP-13 constructed from N-terminal proMMP-13 and C-terminal MMP-19;    MMP-2;    gelatinase A;    MT1-MMP;    membrane type matrix metalloproteinase 1;   

DOI  :  10.1016/S0014-5793(02)03654-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Procollagenase-3 (proMMP-13) can be activated by soluble or cell associated membrane type matrix metalloproteinase 1 (MT1-MMP). In this study we show that the cell based activation of proMMP-13 by MT1-MMP was dependent on the C-terminal domain, as Δ_249–451 proMMP-13, which lacks the haemopexin domain, and a chimaera from N-terminal MMP-13 and C-terminal MMP-19 (proMMP-13/19) were not processed by MT1-MMP expressing cells. Only the initial cleavage at Gly³⁵–Ile³⁶ was dependent on MT1-MMP activity, as conversion to the active enzyme (Tyr⁸⁵ N-terminus) required a functional MMP-13 active site. Unlike proMMP-2 activation, this process was independent of tissue inhibitor of metalloproteinase-2 (TIMP-2) as MT1-MMP expressing cells from the TIMP-2−/− mouse efficiently activated proMMP-13.

【 授权许可】

Unknown