Adhesion & ECM Recombinant Proteins

Matrix metalloproteinases - MMPs

MMPs belong to a family of secreted or membrane-associated zinc endopeptidases capable of digesting extracellular matrix components.^1-2

There are currently more than 25 family members that include collagenases (MMP-1, 8, 13, 18), gelatinases (MMP-2, 9), stromelysins (MMP-3, 10, 19), matrilysins (MMP-7 , 11, 26), and membrane-type MMPs (MMP-14 to 17, 24, 25).

MMPs are produced as pro-enzymes, which require an activation step to release the active MMPs. MMPs activity can be measured using FRET-based assays.

MMP-1 (collagenase-1) is involved in tumor development, metastasis and rheumatoid arthritis.^3-5 MMP-1 is proposed as a therapeutic target for these diseases. It digests a broad range of substrates, including α-1 antitrypsin, myelin basic protein, collagen I, II, III, VII, VIII, casein, gelatin, and others. ^3-5

MMP-9 (92-kDa gelatinase, collagenase-IV) is involved in a number of diseases such as cancer, angiogenesis, alopecia, and metastasis. ^6-7 MMP-9 is secreted as zymogen with prodomain, gelatin-binding domain consisting of three contiguous fibronectin type II units, catalytic domain, proline-rich linker region, and C-terminal hemopexin-like domain. It can degrade a variety of substrates, including gelatin, collagens type IV, V, XIV, a2-macroglobulin, elastin, vitronectin, and proteoglycans.^1,2,6,7

MMP-12 (macrophage elastase) is involved in smoke-induced emphysema, tumor and other diseases. ^8-9 MMP-12 is secreted as a 54-kDa zymogen and becomes the mature 45-kDa active form after proteolytic cleavage. MMP-12 has a broad range of substrates, including α-1 proteinase inhibitor, α-2 antiplasmin, plasminogen activator inhibitor-2, collagen IV, laminin, fibronectin, elastin, but not interstitial collagens.^8-9.

References

1. Woessner, J. et al. J. Biol. Chem. 263, 16918 (1988)
2. Woessner, J. FASEB J. 5, 2145 (1991)
3. Goldberg G. I. et al. Ann. N.Y. Acad. Sci. 580, 375 (1990)
4. Stetler-Stevenson, WG. et al. Annu. Rev. Cell Biol. 9, 541 (1993)
5. Gravallese, EM. et al. Arthritis Rheum. 34, 1076 (1991)
6. Wilhelm, SM. et al. J. Biol.Chem. 264, 17213 (1989)
7. Fosang, AJ. et al., Biochem.J. 295, 273 (1993)
8. Hautamaki, D. et al. Science 277, 2002 (1997)
9. Dong, Z. et al. Cell 88, 801 (1997)