Inflammation dampened by gelatinase A cleavage of monocyte chemoattractant protein-3.
Tissue degradation by the matrix metalloproteinase gelatinase A is pivotal to inflammation and metastases. Recognizing the catalytic importance of substrate-binding exosites outside the catalytic domain, we screened for extracellular substrates using the gelatinase A hemopexin domain as bait in the yeast two-hybrid system. Monocyte chemoattractant protein-3 (MCP-3) was identified as ... a physiological substrate of gelatinase A. Cleaved MCP-3 binds to CC-chemokine receptors-1, -2, and -3, but no longer induces calcium fluxes or promotes chemotaxis, and instead acts as a general chemokine antagonist that dampens inflammation. This suggests that matrix metalloproteinases are both effectors and regulators of the inflammatory response.
Mesh Terms:
Animals, Calcium, Catalytic Domain, Cell Line, Chemokine CCL7, Chemokines, Chemotaxis, Leukocyte, Collagen, Cytokines, Enzyme Activation, Gene Library, Hemopexin, Humans, Inflammation, Mass Spectrometry, Matrix Metalloproteinase 2, Mice, Monocyte Chemoattractant Proteins, Protein Binding, Protein Structure, Tertiary, Receptors, Chemokine, Recombinant Proteins, Tissue Inhibitor of Metalloproteinase-2, Two-Hybrid System Techniques
Animals, Calcium, Catalytic Domain, Cell Line, Chemokine CCL7, Chemokines, Chemotaxis, Leukocyte, Collagen, Cytokines, Enzyme Activation, Gene Library, Hemopexin, Humans, Inflammation, Mass Spectrometry, Matrix Metalloproteinase 2, Mice, Monocyte Chemoattractant Proteins, Protein Binding, Protein Structure, Tertiary, Receptors, Chemokine, Recombinant Proteins, Tissue Inhibitor of Metalloproteinase-2, Two-Hybrid System Techniques
Science
Date: Aug. 18, 2000
PubMed ID: 10947989
View in: Pubmed Google Scholar
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