Progelatinase B Forms from Human Neutrophils. Complex Formation of Monomer/Lipocalin with TIMP-1

Kolkenbrock, Hansjörg; Hecker-Kia, Adelheid; Orgel, Dagmar; Kinawi, Abdelwahab; Ulbrich, Norbert

doi:10.1515/bchm3.1996.377.7-8.529

Cited by 18 publications

(18 citation statements)

References 18 publications

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“…There are however characteristics that are somewhat different between the pro-MMP-9 monomer and homodimer, because the monomer is more rapidly activated by MMP-3 than the homodimer (32). In its heterodimer form with neutrophil gelatinase-associated lipocalin, pro-MMP-9 can bind TIMP-1 and form a ternary complex (49). Activation of the enzyme with plasma kallikrein and HgCl 2 is enhanced in the pro-MMP9⅐neutrophil gelatinase-associated lipocalin complex (50), and the enzyme is protected from degradation (51).…”

Section: Mmp-9 Dimers and Complexes Have Altered Biochemical Charactementioning

confidence: 99%

Interaction of Pro-matrix Metalloproteinase-9/Proteoglycan Heteromer with Gelatin and Collagen

Malla

Berg

Uhlin‐Hansen

et al. 2008

Journal of Biological Chemistry

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Previously we have shown that THP-1 cells synthesize matrix metalloproteinase-9 (MMP-9) where a fraction of the enzyme is strongly linked to a proteoglycan (PG) core protein. In the present work we show that these pro-MMP-9⅐PG heteromers have different biochemical properties compared with the monomeric form of pro-MMP-9. In these heteromers, the fibronectin II-like domain in the catalytic site of the enzyme is hidden, and the fibronectin II-like-mediated binding to gelatin and collagen is prevented. However, a fraction of the pro-MMP-9⅐PG heteromers interacted with gelatin and collagen. This interaction was not through the chondroitin sulfate (CS) part of the PG molecule but, rather, through a region in the PG core protein, a new site induced by the interaction of pro-MMP-9 and the PG core protein, or a non-CS glycosaminoglycan part of the PG molecule. The interaction between pro-MMP-9⅐PG heteromers and gelatin was weaker than the interaction between pro-MMP-9 and gelatin. In contrast, collagen I bound to pro-MMP-9⅐PG heteromers and pro-MMP-9 with approximately the same affinity. Removal of CS chains from the PG part of the heteromers did not affect the binding to gelatin and collagen. Although the identity of the PG core protein is not known, this does not have any impact on the described biochemical properties of the heteromer or its pro-MMP-9 component. It is also shown that a small fraction of the PG, which is not a part of the pro-MMP-9⅐PG heteromer, can bind gelatin. As for the pro-MMP-9⅐PG heteromers, this was independent of the CS chains. The structure that mediates the binding of free PG to gelatin is different from the corresponding structure in the pro-MMP-9⅐PG heteromer, because they were eluted from gelatin-Sepharose columns under totally different conditions. Although only a small amount of pro-MMP-9⅐PG heteromer is formed, the heteromer may have fundamental physiological importance, because only catalytic amounts of the enzyme are required to digest physiological targets.A large number of genetically unrelated proteins are known to contain highly negatively charged glycosaminoglycan (GAG) 2 chains. Such core proteins, substituted with GAG chains, constitute an entity of glycoproteins called proteoglycans (PGs). There are several types of GAG chains, where chondroitin sulfate (CS) and heparin/heparan sulfate (HS) are two major types (1). All GAG chains are unbranched, and they contain a variable number of negatively charged sulfate groups that are important for their function (2). Some PGs are associated with cells, whereas others are secreted and are a part of the extracellular matrix (ECM). Almost all mammalian cells synthesize PGs. Monocytes and macrophages synthesize PGs, which are mainly substituted with CS chains (CSPG) and only a minor proportion of HS (3, 4). In resting monocytes most of the CSPG is not released but sorted to the endocytic pathway and degraded (4). However, when monocytes are stimulated and differentiated to macrophages, both the biosynthesis and the secretion of CSPG are i...

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Section: Mmp-9 Dimers and Complexes Have Altered Biochemical Charactementioning

confidence: 99%

Interaction of Pro-matrix Metalloproteinase-9/Proteoglycan Heteromer with Gelatin and Collagen

Malla

Berg

Uhlin‐Hansen

et al. 2008

Journal of Biological Chemistry

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“…Active enzyme can be eluted with NaCl as follows: MMP-1, 0.7 M (36); MMP-3, Ͻ0.1 M (36); human MMP-7, 0.5 M (37); and rat MMP-13, 0.8 M (38). Results for zymogen forms are: proMMP-2, 0.3 M (39); proMMP-8, 0.2 M (40); and proMMP-9, 0.12 M (41). No one has studied both forms of one enzyme.…”

Section: Heparin and Related Compounds But Not Protamine Enhance Mamentioning

confidence: 99%

Heparan Sulfate Proteoglycans as Extracellular Docking Molecules for Matrilysin (Matrix Metalloproteinase 7)

Woessner

2000

Journal of Biological Chemistry

218

189

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“…TIMP-1 binds to progel B, which is secreted as a monomer or dimer, or in disulfide-mediated linkage with neutrophil gelatinase-associated lipocalin (NGAL) to form a ternary complex of progel B monomer, TIMP-1 and NGAL (progel B-TIMP-1-NGAL) (14,15). Unbound TIMP-1 may be inactivated in vitro by cleavage, degradation, or chemical modification via proteolytic and nonproteolytic mechanisms involving serine or thiol proteases and reactive oxygen species, respectively (16 -19).…”

mentioning

confidence: 99%

Mast Cell Tissue Inhibitor of Metalloproteinase-1 Is Cleaved and Inactivated Extracellularly by α-Chymase

Frank

Rossall

Caughey

et al. 2001

The Journal of Immunology

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We previously reported that mast cell α-chymase cleaves and activates progelatinase B (progel B). Outside of cells, progel B is complexed with tissue inhibitor of metalloproteinase (TIMP)-1, which hinders zymogen activation and inhibits activity of mature forms. The current work demonstrates that dog BR mastocytoma cells, HMC-1 cells, and murine bone marrow-derived mast cells secrete TIMP-1 whose electrophoretic profile in supernatants suggests degranulation-dependent proteolysis. α-Chymase cleaves uncomplexed TIMP-1, reducing its ability to inhibit gel B, whereas tryptase has no effect. Sequencing of TIMP-1’s α-chymase-mediated cleavage products reveals hydrolysis at Phe12-Cys13 and Phe23-Val24 in loop 1 and Phe101-Val102 and Trp105-Asn106 in loop 3 of the NH2-terminal domain. TIMP-1 in a ternary complex with progel B and neutrophil gelatinase-associated lipocalin is also susceptible to α-chymase cleavage, yielding products like those resulting from processing of free TIMP-1. Thus, α-chymase cleaves free and gel B-bound TIMP-1. Incubation of the progel B-TIMP-1-neutrophil gelatinase-associated lipocalin complex with α-chymase increases gel B activity 2- to 5-fold, suggesting that α-chymase activates progel B whether it exists as free monomer or as a complex with TIMP-1. Furthermore, inhibition of α-chymase blocks degranulation-induced TIMP-1 processing (absent in α-chymase-deficient HMC-1 cells). Purified α-chymase processes TIMP-1 in BR supernatants, generating products like those induced by degranulation. In summary, these results suggest that controlled exocytosis of mast cell α-chymase activates progel B even in the presence of TIMP-1. This is the first identification of a protease that overcomes inhibition by bound TIMP-1 to activate progel B without involvement of other proteases.

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Progelatinase B Forms from Human Neutrophils. Complex Formation of Monomer/Lipocalin with TIMP-1

Cited by 18 publications

References 18 publications

Interaction of Pro-matrix Metalloproteinase-9/Proteoglycan Heteromer with Gelatin and Collagen

Interaction of Pro-matrix Metalloproteinase-9/Proteoglycan Heteromer with Gelatin and Collagen

Heparan Sulfate Proteoglycans as Extracellular Docking Molecules for Matrilysin (Matrix Metalloproteinase 7)

Mast Cell Tissue Inhibitor of Metalloproteinase-1 Is Cleaved and Inactivated Extracellularly by α-Chymase

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