Table 1.
Mechanisms of cell surface binding of proteinases
Binding mechanism | Proteinases bound | Cell types | Proteolytic Activities |
---|---|---|---|
Transmembrane Domain | MT1-MMP
MT2-MMP MT3-MMP MT5-MMP |
Epithelial cells
Tumor cells Fibroblasts Macrophages |
ECM degradation, tumor invasiveness
Pro-MMP-2 &-13 binding and activation, TNF-α activation, proteinase inhibitor degradation |
ADAMs | Epithelial cells
Endothelial cells Fibroblasts Smooth muscle cells Inflammatory cells Tumor cells |
Shedding of membrane- associated cytokines, apoptosis ligands, growth factors and receptors for these molecules
Pro-urokinase activation |
|
Type II serine proteases(matriptase) | Monocytes, B lymphocytes | ||
GPI anchor | uPAR and urokinase | PMN mononuclear phagocytes
Fibroblasts Epithelial cells Smooth muscle cells |
Fibrinolysis Activation of latent growth factors & proMMPs |
MT4-MMP | CNS eosinophils | ECM degradation proMMP-2 activation | |
MT6-MMP | PMN | ECM degradation | |
Proteoglycans | Pro- and active MMP-2, -7, -9, and -13 | Uterine epithelial cells | ECM degradation Host defense |
NE, CG, PR3 | PMN, macrophages | Wound healing Inflammation | |
Integrins | β2: Pro-MMP-9 & -8, NE, CG | PMN | Unknown |
α2β1: MMP-1 | Keratinocytes | Cell migration | |
αvβ3: MMP-2 | Endothelial cells & melanoma cells | Tumor invasiveness and neovascularization | |
TIMP-2 | Pro-MMP-2 and proMMP-13 | Fibroblasts Endothelium
Tumor cells |
ECM degradation
Tumor invasiveness |
CD44 | MMP -2 & MMP-9 | Tumor cells & keratinocytes | ECM degradation, activation of latent TGF-β |
MMP-7 | Tumor cells & epithelial cells | Post partum uterine involution, and lactation through HB-EGF shedding | |
Tissue factor | Factor VII | Monocytes/macrophages | Activation of actor VII and other serine proteases involved in thrombosis |
High-molecular- weight Kininogen | Prekallirein | Endothelial cells | Factor XI activation leading to thrombosis
Bradykinin generation Pro-urokinase activation |
P11 | Cathepsin B | Tumor cells | Tumor growth and metastasis |
Unknown | Cathepsin B | Macrophages, CTLs | Elastin degradation, degradation of perforins |
Legend for Table 1. ECM, extracellular matrix; PMN, polymorphonuclear neutrophils; TNF-α, tumor necrosis factor- α; GPI, glycosyl phosphatidyl inositol; CNS, central nervous system; NE, neutrophil elastase; CG, cathepsin G; PR3, proteinase 3; TGF-β, transforming growth factor- β, HB-EGF, heparin binding epidermal growth factor; CTLs, cytotoxic T lymphocytes