Activation of the extracellular signal‐regulated protein kinase (ERK) cascade by membrane‐type‐1 matrix metalloproteinase (MT1‐MMP)

FEBS Letters

Gingras, Denis¹  Bousquet-Gagnon, Nathalie¹  Annabi, Borhane¹  Béliveau, Richard¹  Lachambre, Marie-Paule¹  Langlois, Stéphanie¹ 

[1] Laboratoire de Médecine Moléculaire Ste-Justine-UQAM, Centre de Cancérologie Charles-Bruneau, Hôpital Ste-Justine et Université du Québec à Montréal, C.P. 8888, Succ. Centre-ville, Montreal, QC, Canada H3C 3P8

关键词: Membrane-type-1 matrix metalloproteinase;    Migration;    Extracellular signal-regulated protein kinase;    Signal transduction;    ERK;    extracellular signal-regulated protein kinase;    MMP;    matrix metalloproteinase;    MT-MMP;    membrane-type matrix metalloproteinase;    TIMP;    tissue inhibitor of matrix metalloproteinase;   

DOI  :  10.1016/S0014-5793(01)02985-4

学科分类：生物化学/生物物理

来源: John Wiley & Sons Ltd.

【 摘 要 】

The mechanisms underlying membrane-type-1 matrix metalloproteinase (MT1-MMP)-dependent induction of cell migration were investigated. Overexpression of MT1-MMP induced a marked increase in cell migration, this increase being dependent on the presence of the cytoplasmic domain of the protein. MT1-MMP-dependent migration was inhibited by a mitogen-activated protein kinase kinase 1 inhibitor, suggesting the involvement of the extracellular signal-regulated protein kinase (ERK) cascade in the induction of migration. Accordingly, MT1-MMP overexpression induced the activation of ERK, this process being also dependent on the presence of its cytoplasmic domain. MT1-MMP-induced activation of both migration and ERK required the catalytic activity of the enzyme as well as attachment of the cells to matrix proteins. The MT1-MMP-dependent activation of ERK was correlated with the activation of transcription through the serum response element, whereas other promoters were unaffected. Taken together, these results indicate that MT1-MMP trigger important changes in cellular signal transduction events, leading to cell migration and to gene transcription, and that these signals possibly originate from the cytoplasmic domain of the protein.

【 授权许可】

Unknown