Cell surface activation of progelatinase A (proMMP-2) and cell migration.
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.
Nagase
H
H
Department of Biochemistry and Molecular Biology, University of Kansas Medical Center, Kansas City 66160, USA. hnagase@kumc.edu
D000818:Animals; D002462:Cell Membrane / Q000201:enzymology*; D002465:Cell Movement / Q000502:physiology*; D004789:Enzyme Activation; D004792:Enzyme Precursors / Q000378:metabolism*; D005057:Eukaryotic Cells / Q000166:cytology / Q000201:enzymology; D018093:Gelatinases / Q000378:metabolism*; D006801:Humans; D008666:Metalloendopeptidases / Q000378:metabolism*; D019716:Tissue Inhibitor of Metalloproteinase-2 / Q000378:metabolism
D004792:Enzyme Precursors; D019716:Tissue Inhibitor of Metalloproteinase-2; D018093:Gelatinases; D008666:Metalloendopeptidases; C069860:progelatinase