Publication Date:
2000-08-19
Description:
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.〈br /〉〈span class="detail_caption"〉Notes: 〈/span〉McQuibban, G A -- Gong, J H -- Tam, E M -- McCulloch, C A -- Clark-Lewis, I -- Overall, C M -- New York, N.Y. -- Science. 2000 Aug 18;289(5482):1202-6.〈br /〉〈span class="detail_caption"〉Author address: 〈/span〉Department of Biochemistry and Molecular Biology, Biomedical Research Centre, University of British Columbia, Vancouver, BC V6T 1Z3, Canada.〈br /〉〈span class="detail_caption"〉Record origin:〈/span〉 〈a href="http://www.ncbi.nlm.nih.gov/pubmed/10947989" target="_blank"〉PubMed〈/a〉
Keywords:
Animals
;
Calcium/metabolism
;
Catalytic Domain
;
Cell Line
;
Chemokine CCL7
;
Chemokines/antagonists & inhibitors/metabolism
;
Chemotaxis, Leukocyte
;
Collagen/metabolism
;
*Cytokines
;
Enzyme Activation
;
Gene Library
;
Hemopexin/chemistry/metabolism
;
Humans
;
Inflammation/*metabolism/pathology
;
Mass Spectrometry
;
Matrix Metalloproteinase 2/chemistry/*metabolism
;
Mice
;
Monocyte Chemoattractant Proteins/*metabolism
;
Protein Binding
;
Protein Structure, Tertiary
;
Receptors, Chemokine/antagonists & inhibitors/metabolism
;
Recombinant Proteins/metabolism
;
Tissue Inhibitor of Metalloproteinase-2/metabolism
;
Two-Hybrid System Techniques
Print ISSN:
0036-8075
Electronic ISSN:
1095-9203
Topics:
Biology
,
Chemistry and Pharmacology
,
Computer Science
,
Medicine
,
Natural Sciences in General
,
Physics
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