Proteolytic activation of the precursor of membrane type 1 matrix metalloproteinase by human plasmin

FEBS Letters

Kido, Hiroshi¹  Okumura, Yuushi¹  Seiki, Motoharu²  Sato, Hiroshi² 

[1] Division of Enzyme Chemistry, Institute for Enzyme Research, The University of Tokushima, Tokushima 770, Japan;Department of Molecular Virology and Oncology, Cancer Research Institute, Kanazawa University, Kanazawa, Ishikawa 920, Japan

关键词: Membrane type 1 matrix metalloproteinase;    Plasmin;    Zymogen convertase;    Pro-gelatinase A;    pro-MT1-MMP;    precursor of membrane type 1 matrix metalloproteinase;    dec;    decanoyl;    cmk;    chloromethyl ketone;    mAb;    monoclonal antibody;    Boc;    N-tert-butyloxycarbonyl;    MCA;    4-methyl-coumaryl-7-amide;    Pyr;    l-pyroglutamyl;    SDS-PAGE;    sodium dodecyl sulfate-polyacrylamide gel electrophoresis;    GST;    glutathione S-transferase;    pro-gelatinase A;    precursor of gelatinase A;    uPA;    urokinase-type plasminogen activator;    PBS;    phosphate-buffered saline;   

DOI  :  10.1016/S0014-5793(96)01523-2

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

Membrane type 1 matrix metalloproteinase (MT1-MMP) was suggested to play a critical role in the regulation of tissue invasion by normal and neoplastic cells by directly mediating the activation of pro-gelatinase A. Recently, the proteolytic activation of a pro-MT1-MMP by an intracellular proprotein convertase, furin, was reported. In this study, we found that plasmin efficiently activates the pro-MT1-MMP by cleaving immediately downstream of Arg¹⁰⁸ and Arg¹¹¹ in the multi-basic motif between its pro- and catalytic domains that participates in the activation of pro-gelatinase A. Our present data suggest that pro-MT1-MMP transported to the plasma membrane is activated by plasmin extracellularly and thus it may play an important role in the matrix degradation process.

【 授权许可】

Unknown