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chemokine-like factor superfamily member 5
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[matrix metalloproteinase-9] This enzyme (EC184.108.40.206) is known variously as gelatinase B, 92 kDa gelatinase, 92 kDa type IV collagenase, or PMNL gelatinase (polymorphonuclear leukocyte gelatinase), gelatinase type IV-B, collagenase type 5 (collagenase-5; abbr. also CL-5).
Yu and Woessner (2000) have reported that MMP-9 is tightly bound to tissues and utilizes heparan sulfate proteoglycans as extracellular docking molecules. Bar-Or et al (2003) have observed high expression of the metalloproteinase in monocytes. Noirey et al (2002) have reported that MMP-9 is produced by Langerhans cells following cell activation. Walker et al (2006) have reported expression of MMP-9 by microglial cells. Hughes et al (2002) have reported that MMP-9 is produced by Schwann cells, endothelial cells, and macrophages during Wallerian degeneration.
Ashworth et al (1999) have reported that MMP-9 degrades fibrillin, the principal structural component of the 10-12 nm diameter elastic microfibrils of the extracellular matrix.
Patterson and Sang (1997) have implicated MMP-7 in the regulation of blood vessel formation by showing that MMP-7 hydrolyzes human plasminogen to generate angiostatin, one of the most potent inhibitors of angiogenesis.
MMP-9 has been shown to degrade substance P, angiotensin-1, but not angiotensin-2 (Diekmann and Tschesche, 1994).
The CXC-Chemokines CTAP-3, PF4, and GRO-alpha are degraded by MMP-9, whereas RANTES and MCP-2 are resistant (Van den Steen et al, 2000). Van den Steen et al (2000) have reported that the metalloproteinase MMP-9 truncates the 77 amino acid form of IL8 at the N-terminus, yielding a protein that has a much higher potency in neutrophil activation due to enhanced binding to, and signaling through, the type-1 IL8 receptor CXCR1). The effect is less pronounced with the type-2 IL8 receptor. Van Den Steen et al (2003) have reported that MMP-9 processes the chemokines human GCP-2 (CXCL6), ENA-78 (CXCL5) and mouse GCP-2 (LIX) and modulates their physiological activities. This cleavage can potentiate chemokine activity by first generating more potent truncated forms of the protein and finally generates inactive fragments. Belaaouaj et al (2000) have reported that MMP-9 degrades TFPI-1 [tissue factor pathway inhibitor-1] and thus may effect coagulation mediated by tissue factor.
Gearing et al (1995) have reported that MMP-9 can cleave a recombinant pro-TNF substrate to yield mature TNF-alpha.
Levesque et al (2003) have reported that MMP-9 can degrade the SCF receptor (kit) on the surface of hematopoietic progenitor cells.
Takino et al (2003) have reported that MMP-9 cleaves the metastasis suppressor protein KISS-1 and also Metastin, which is derived from KISS-1.
Roeb et al (2002) have shown that the hemopexin domain of MMP-9 is a gelatin binding domain. The recombinant domain is able to block MMP-9 activity and tumor cell invasion (Burg-Roderfeld et al, 2007). Van den Steen et al (2006) have shown that the hemopexin domain of MMP-9 contains binding sites for the LRP-1 and LRP-2 receptors. Interaction with these receptors can mediate the endocytosis and catabolism of the enzyme and downregulates bioavailability. A unique linker sequence of approximately 64 amino acid that precedes the hemopexin domain is required to correctly orient the hemopexin domain for inhibition by TIMP-1 and receptor-mediated internalization. Mantuano et al (2008) have shown that the hemopexin domain of MMP-9 activates cell signaling and promotes migration of Schwann cells by binding to LRP-1. Montferran et al (2004) have shown that the hemopexin domain of MMP-9 is important for the interactions of the metalloproteinase with the Ku heterodimer (Ku70/Ku80), a protein that plays a central role in DNA double-strand breaks repair but is expressed also on the cell surface of different cell types. Interactions of Ku and MMP-9 are observed at at the cell membrane of highly invasive hematopoietic cells of normal and tumoral origin and are involved in remodelling of the extracellular matrix. Geurts et al (2008) have reported that the hemopexin domain of MMP-9 reacts with hemin or beta-hematin, the core constituent of hemozoin or malaria pigment. This provokes autocatalytic processing of the propeptide, thereby priming activation by MMP-3. Ezhilarasan et al (2009) have demonstrated that the MMP-9 hemopexin domain inhibits angiogenesis features of endothelial cells and retards the growth of intracranial glioblastoma xenografts in nude mice.
For other entries pertaining to metalloproteinases see also the Metalloproteinase Dictionary section of this encyclopedia.
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