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Sammanfattning

Mast cell tryptase is stored as an active tetramer in complex with heparin in mast cell secretory granules. Previously, we demonstrated the dependence on heparin for the activation/tetramer formation of a recombinant tryptase. Here we have investigated the structural requirements for this activation process. The ability of heparin-related saccharides to activate a recombinant murine tryptase, mouse mast cell protease-6 (mMCP-6), was strongly dependent on anionic charge density and size. The dose-response curve for heparin-induced mMCP-6 activation displayed a bell-shaped appearance, indicating that heparin acts by binding to more than one tryptase monomer simultaneously. The minimal heparin oligosaccharide required for binding to mMCP-6 was 8-10 saccharide units. Gel filtration analyses showed that such short oligosaccharides were unable to generate tryptase tetramers, but instead gave rise to active mMCP-6 monomers. The active monomers were inhibited by bovine pancreatic trypsin inhibitor, whereas the tetramers were resistant. Furthermore, monomeric (but not tetrameric) mMCP-6 degraded fibronectin. Our results suggest a model for tryptase tetramer formation that involves bridging of tryptase monomers by heparin or other highly sulfated polysaccharides of sufficient chain length. Moreover, our results raise the possibility that some of the reported activities of tryptase may be related to active tryptase monomers that may be formed according to the mechanism described here.

Publicerad i

Journal of Biological Chemistry
2001, volym: 276, nummer: 46, sidor: 42774-42781
Utgivare: AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

SLU författare

  • Hallgren, Jenny

    • Institutionen för veterinärmedicinsk kemi, Sveriges lantbruksuniversitet

  • Pejler, Gunnar

    • Institutionen för veterinärmedicinsk kemi, Sveriges lantbruksuniversitet

Associerade SLU-program

Framtidens djurhälsa och djurvälfärd (tom Jan 2017)

UKÄ forskningsämne

Immunologi

Publikationens identifierare

  • DOI: https://doi.org/10.1074/jbc.M105531200

Permanent länk till denna sida (URI)

https://res.slu.se/id/publ/66605