MINIREVIEWS
Cell Research (1998)8:179-186
© 1998 SIBS, CAS All rights reserved 1001-0602/98
Cell surface activation of progelatinase A (proMMP-2) and cell
migration.
Nagase H.
Department of Biochemistry and Molecular Biology, University of Kansas
Medical Center, Kansas City 66160, USA.
Gelatinase A (MMP-2) is considered to play a critical role in cell migration
and invasion. The proteinase is secreted from the cell as an inactive zymogen.
In vivo it is postulated that activation of progelationase A (proMMP-2)
takes place on the cell surface mediated by membrane-type matrix metalloproteinases
(MT-MMPs). Recent studies have demonstrated that proMMP-2 is recruited to
the cell surface by interacting with tissue inhibitor of metalloproteinases-2
(TIMP-2) bound to MT1-MMP by forming a ternary complex. Free MT1-MMP closely
located to the ternary complex then activates proMMP-2 on the cell surface.
MT1-MMP is found in cultured invasive cancer cells at the invadopodia. The
MT-MMP/TIMP-2/MMP-2 system thus provides localized expression of proteolysis
of the extracellular matrix required for cell migration.
Keywords : GelatinaseA
MT-MMPs, Cell surface activation, TIMP-2, Extracellular matrix. |
