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Gene Review

Tpsb2  -  tryptase beta 2

Mus musculus

Synonyms: AV011504, MMCP-6, Mast cell protease 6, Mcp-6, Mcp6, ...
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Disease relevance of Mcpt6

  • In further experiments using highly purified enzymes, mastocytoma cell chymase activated 92-kD progelatinase in the absence of other enzymes or cofactors; tryptase and dMCP-3, however, had no effect [1].
  • Tryptase has potent proinflammatory properties and has been implicated in diverse pathological conditions such as asthma and fibrosis [2].
  • Subsequent analysis of a tryptase-specific, phage display peptide library revealed that recombinant mMCP-7 preferentially cleaves an amino acid sequence that is nearly identical to that in the middle of the alpha-chain of rat fibrinogen [3].
  • Because enzymatically active mMCP-7 is selectively released into the plasma of V3 mastocytosis mice undergoing passive systemic anaphylaxis, we used this in vivo model system to identify a physiologic substrate of the tryptase [3].
  • CONCLUSION: The discovery that the human genome contains a large number of homologous, but distinct, tryptase genes suggests that the individual members of this family of proteases evolved to carry out discrete functions in mast cell-mediated allergic reactions [4].

High impact information on Mcpt6

  • Mast cells infiltrate hyperplasias, dysplasias, and invasive fronts of carcinomas, but not the core of solid tumors, where they degranulate in close apposition to capillaries and epithelial basement membranes, releasing mast-cell-specific serine proteases MCP-4 (chymase) and MCP-6 (tryptase) [5].
  • Testing of individual mast cell-derived products in this model indicated that tumor necrosis factor was the main mediator of nodal hypertrophy, whereas tryptase and histamine had no effect [6].
  • This plasma-localized tryptase was approximately 150 kD in its multimeric state and approximately 32 kD in its monomeric state, possessed an NH2 terminus identical to that of mature mMCP-7, and was not covalently bound to any protease inhibitor [7].
  • Inhibitors of tryptase and dog mast cell protease (dMCP)-3, i.e., aprotinin or bis(5-amidino-2-benzimidazolyl) methane (BABIM), did not [1].
  • Analysis of mRNA from multiple sclerosis lesions revealed increased amounts of transcripts for several genes encoding molecules traditionally associated with allergic responses, including prostaglandin D synthase, histamine receptor type 1 (H1R), platelet activating factor receptor, Ig Fc epsilon receptor 1 (Fc epsilon RI), and tryptase [8].

Chemical compound and disease context of Mcpt6


Biological context of Mcpt6


Anatomical context of Mcpt6


Associations of Mcpt6 with chemical compounds

  • Because MMCP-5 is a chymase and MMCP-6 a tryptase, there was a possibility that the difference in regulation mechanisms was associated with their different characteristics as proteases [17].
  • The minimal heparin oligosaccharide required for binding to mMCP-6 was 8-10 saccharide units [18].
  • Analysis of the tryptase family of genes in mice and humans now indicates that a primordial serine protease gene duplicated early and often during the evolution of mammals to generate a panel of homologous tryptases in each species that differ in their tissue expression, substrate specificities, and physical properties [21].
  • The dysregulated tryptase in SOCS1-/- BMMCs is unlikely to be mMCP6 or mMCP7, because the enzyme activity was not inhibited by Polybrene but was inhibited by normal mouse plasma [22].
  • The proteolytic activity in SOCS1-/- BMMCs was selectively inhibited by phenylmethylsulfonyl fluoride and soybean trypsin inhibitor, suggesting that the protease regulated by SOCS1 is a tryptase [22].

Regulatory relationships of Mcpt6

  • On the other hand, dystrophin-positive normal controls injected with 48/80 liberated little CK or tryptase activity [23].
  • These results show that c-jun might play a role in regulating the transcription of mMCP-6 gene in mast cells stimulated by SCF [24].
  • A second implantation serine proteinase gene (ISP2) was isolated, which encodes a related secreted tryptase expressed specifically within uterine endometrial glands [25].

Other interactions of Mcpt6


Analytical, diagnostic and therapeutic context of Mcpt6


  1. Dog mastocytoma cells secrete a 92-kD gelatinase activated extracellularly by mast cell chymase. Fang, K.C., Raymond, W.W., Lazarus, S.C., Caughey, G.H. J. Clin. Invest. (1996) [Pubmed]
  2. Histidines are critical for heparin-dependent activation of mast cell tryptase. Hallgren, J., Bäckström, S., Estrada, S., Thuveson, M., Pejler, G. J. Immunol. (2004) [Pubmed]
  3. The tryptase, mouse mast cell protease 7, exhibits anticoagulant activity in vivo and in vitro due to its ability to degrade fibrinogen in the presence of the diverse array of protease inhibitors in plasma. Huang, C., Wong, G.W., Ghildyal, N., Gurish, M.F., Sali, A., Matsumoto, R., Qiu, W.T., Stevens, R.L. J. Biol. Chem. (1997) [Pubmed]
  4. Cloning of the human homolog of mouse transmembrane tryptase. Wong, G.W., Tang, Y., Stevens, R.L. Int. Arch. Allergy Immunol. (1999) [Pubmed]
  5. Inflammatory mast cells up-regulate angiogenesis during squamous epithelial carcinogenesis. Coussens, L.M., Raymond, W.W., Bergers, G., Laig-Webster, M., Behrendtsen, O., Werb, Z., Caughey, G.H., Hanahan, D. Genes Dev. (1999) [Pubmed]
  6. Mast cell-derived tumor necrosis factor induces hypertrophy of draining lymph nodes during infection. McLachlan, J.B., Hart, J.P., Pizzo, S.V., Shelburne, C.P., Staats, H.F., Gunn, M.D., Abraham, S.N. Nat. Immunol. (2003) [Pubmed]
  7. Fate of two mast cell tryptases in V3 mastocytosis and normal BALB/c mice undergoing passive systemic anaphylaxis: prolonged retention of exocytosed mMCP-6 in connective tissues, and rapid accumulation of enzymatically active mMCP-7 in the blood. Ghildyal, N., Friend, D.S., Stevens, R.L., Austen, K.F., Huang, C., Penrose, J.F., Sali, A., Gurish, M.F. J. Exp. Med. (1996) [Pubmed]
  8. Multiple elements of the allergic arm of the immune response modulate autoimmune demyelination. Pedotti, R., DeVoss, J.J., Youssef, S., Mitchell, D., Wedemeyer, J., Madanat, R., Garren, H., Fontoura, P., Tsai, M., Galli, S.J., Sobel, R.A., Steinman, L. Proc. Natl. Acad. Sci. U.S.A. (2003) [Pubmed]
  9. Dog mastocytoma tryptase: affinity purification, characterization, and amino-terminal sequence. Caughey, G.H., Viro, N.F., Ramachandran, J., Lazarus, S.C., Borson, D.B., Nadel, J.A. Arch. Biochem. Biophys. (1987) [Pubmed]
  10. Temporal distribution of distinct mast cell phenotypes during intestinal schistosomiasis in mice. De Jonge, F., Van Nassauw, L., Van Meir, F., Miller, H.R., Van Marck, E., Timmermans, J.P. Parasite Immunol. (2002) [Pubmed]
  11. Cloning and expression of the dog mast cell alpha-chymase gene. Caughey, G.H., Blount, J.L., Koerber, K.L., Kitamura, M., Fang, K.C. J. Immunol. (1997) [Pubmed]
  12. Mast cell inhibitor cromolyn increases blood clotting and hypoxia in murine breast cancer. Samoszuk, M., Corwin, M.A. Int. J. Cancer (2003) [Pubmed]
  13. Mast cell tryptase degrades HDL and blocks its function as an acceptor of cellular cholesterol. Lee, M., Sommerhoff, C.P., von Eckardstein, A., Zettl, F., Fritz, H., Kovanen, P.T. Arterioscler. Thromb. Vasc. Biol. (2002) [Pubmed]
  14. Inhibitory effect of the transcription factor encoded by the mutant mi microphthalmia allele on transactivation of mouse mast cell protease 7 gene. Ogihara, H., Morii, E., Kim, D.K., Oboki, K., Kitamura, Y. Blood (2001) [Pubmed]
  15. Regulation of mouse mast cell protease 6 gene expression by transcription factor encoded by the mi locus. Morii, E., Tsujimura, T., Jippo, T., Hashimoto, K., Takebayashi, K., Tsujino, K., Nomura, S., Yamamoto, M., Kitamura, Y. Blood (1996) [Pubmed]
  16. Abnormal expression of mouse mast cell protease 5 gene in cultured mast cells derived from mutant mi/mi mice. Morii, E., Jippo, T., Tsujimura, T., Hashimoto, K., Kim, D.K., Lee, Y.M., Ogihara, H., Tsujino, K., Kim, H.M., Kitamura, Y. Blood (1997) [Pubmed]
  17. Deficient transcription of mouse mast cell protease 4 gene in mutant mice of mi/mi genotype. Jippo, T., Lee, Y.M., Katsu, Y., Tsujino, K., Morii, E., Kim, D.K., Kim, H.M., Kitamura, Y. Blood (1999) [Pubmed]
  18. Structural requirements and mechanism for heparin-induced activation of a recombinant mouse mast cell tryptase, mouse mast cell protease-6: formation of active tryptase monomers in the presence of low molecular weight heparin. Hallgren, J., Spillmann, D., Pejler, G. J. Biol. Chem. (2001) [Pubmed]
  19. Up-regulation of mouse mast cell protease-6 gene by transforming growth factor-beta and activin in mast cell progenitors. Funaba, M., Ikeda, T., Murakami, M., Ogawa, K., Abe, M. Cell. Signal. (2005) [Pubmed]
  20. Cloning of the cDNA and gene of mouse mast cell protease-6. Transcription by progenitor mast cells and mast cells of the connective tissue subclass. Reynolds, D.S., Gurley, D.S., Austen, K.F., Serafin, W.E. J. Biol. Chem. (1991) [Pubmed]
  21. Identification of a new member of the tryptase family of mouse and human mast cell proteases which possesses a novel COOH-terminal hydrophobic extension. Wong, G.W., Tang, Y., Feyfant, E., Sali, A., Li, L., Li, Y., Huang, C., Friend, D.S., Krilis, S.A., Stevens, R.L. J. Biol. Chem. (1999) [Pubmed]
  22. Suppressor of cytokine signaling 1 regulates an endogenous inhibitor of a mast cell protease. Ilangumaran, S., Finan, D., Raine, J., Rottapel, R. J. Biol. Chem. (2003) [Pubmed]
  23. Enhanced sensitivity of mdx mice to intramuscular injection of compound 48/80. Granchelli, J.A., Hudecki, M.S., Pollina, C.M. Res. Commun. Chem. Pathol. Pharmacol. (1994) [Pubmed]
  24. Requirement of c-jun transcription factor on the mouse mast cell protease-6 expression in the mast cells. Kim, D.K., Lee, Y.M. Arch. Biochem. Biophys. (2004) [Pubmed]
  25. Regulation of the strypsin-related proteinase ISP2 by progesterone in endometrial gland epithelium during implantation in mice. O'Sullivan, C.M., Liu, S.Y., Rancourt, S.L., Rancourt, D.E. Reproduction (2001) [Pubmed]
  26. Transforming and differentiation-inducing potential of constitutively activated c-kit mutant genes in the IC-2 murine interleukin-3-dependent mast cell line. Hashimoto, K., Tsujimura, T., Moriyama, Y., Yamatodani, A., Kimura, M., Tohya, K., Morimoto, M., Kitayama, H., Kanakura, Y., Kitamura, Y. Am. J. Pathol. (1996) [Pubmed]
  27. A possible role of tryptase in angiogenesis in the brain of mdx mouse, a model of Duchenne muscular dystrophy. Nico, B., Marzullo, A., Corsi, P., Vacca, A., Roncali, L., Ribatti, D. Neuroscience (2004) [Pubmed]
  28. Tryptase 4, a new member of the chromosome 17 family of mouse serine proteases. Wong, G.W., Li, L., Madhusudhan, M.S., Krilis, S.A., Gurish, M.F., Rothenberg, M.E., Sali, A., Stevens, R.L. J. Biol. Chem. (2001) [Pubmed]
  29. A closely linked complex of mouse mast cell-specific chymase genes on chromosome 14. Gurish, M.F., Nadeau, J.H., Johnson, K.R., McNeil, H.P., Grattan, K.M., Austen, K.F., Stevens, R.L. J. Biol. Chem. (1993) [Pubmed]
  30. Effect of IL-3 and stem cell factor on the appearance of human basophils and mast cells from CD34+ pluripotent progenitor cells. Kirshenbaum, A.S., Goff, J.P., Kessler, S.W., Mican, J.M., Zsebo, K.M., Metcalfe, D.D. J. Immunol. (1992) [Pubmed]
  31. Purification of mast cell proteases from murine skin. Algermissen, B., Laubscher, J.C., Bauer, F., Henz, B.M. Exp. Dermatol. (1999) [Pubmed]
  32. Expression of a mast cell tryptase in the human monocytic cell lines U-937 and Mono Mac 6. Huang, R., Abrink, M., Gobl, A.E., Nilsson, G., Aveskogh, M., Larsson, L.G., Nilsson, K., Hellman, L. Scand. J. Immunol. (1993) [Pubmed]
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