Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: EC:3.4.24.17 (MMP-3)
 3,419 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

The 33-kDa matrix protein BM-40 (SPARC, osteonectin) consists of an acidic N-terminal domain I, a central cysteine-rich follistatin-like module, and a C-terminal extracellular calcium-binding (EC) module. Previous studies attributed collagen IV and high affinity calcium binding of BM-40 to its EC module, which was shown by x-ray crystallography to consist of an EF-hand pair surrounded by several alpha-helical and loop segments. This module was now shown by surface plasmon resonance assay to bind with similar affinities to collagens I, III, and V. Cleavage of recombinant BM-40 and its EC module by collagenase-3, gelatinases A and B, matrilysin, and stromelysin-1 showed similar fragment patterns, whereas collagenase-1 was inactive. Some differences were, however, observed in cleavage rates and the preference of certain cleavage sites. Edman degradation of fragments demonstrated only three to four major cleavage sites in the central region of domain I and a single uniform cleavage in helix C of the EC module. Cleavage is accompanied by a 7-20-fold increase in binding activity for collagens I, IV, and V but revealed only small effects on calcium-dependent alpha-helical changes in the EC module. The data were interpreted to indicate that helix C cleavage is mainly responsible for enhancing collagen affinity by exposing the underlying helix A of the EC module. A similar activation may also occur in situ as indicated previously for tissue-derived BM-40.
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PMID:Limited cleavage of extracellular matrix protein BM-40 by matrix metalloproteinases increases its affinity for collagens. 908 57

The objective was to investigate the effect of activin A on matrix metalloproteinase 3 (MMP-3) production and to identify the role of activin A in chondroprotection. SW1353 cells, a human chondrosarcoma cell line, were stimulated with interleukin (IL) 1alpha and tumor necrosis factor (TNF) alpha, and the concentrations of activin A, follistatin, and MMP-3 secreted into the culture media were measured by enzyme-linked immunosorbent assay (ELISA). Activin A was added to cell cultures in the presence of IL-1alpha or TNFalpha to determine its effect on the production of MMP-3 and sulfated glycosaminoglycan (sGAG) (measured by Alcian blue assay). To study the mechanism responsible for the chondroprotective effects of activin A, the production of IL-1 receptor antagonist (IL-1ra) and tissue inhibitor for metalloproteinases 1 (TIMP-1) was examined by ELISA. Addition of IL-1alpha did not affect the production of activin A by cultured SW1353 cells. IL-1alpha and activin A inhibited the production of follistatin. Stimulation of SW1353 cells with activin A suppressed IL-1alpha-induced, but not TNFalpha-induced, MMP-3 expression. Activin A had no effect on the production of sGAG, IL-1ra, or TIMP-1, although it suppressed the induction of TIMP-1 and IL-1ra by IL-1alpha. This novel finding of MMP-3 inhibition by activin A suggests a new role of activin A in cartilage remodeling. Activin A may have therapeutic potential for preventing cartilage degradation.
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PMID:Activin A suppresses interleukin-1-induced matrix metalloproteinase 3 secretion in human chondrosarcoma cells. 1743