Regulation and Physiological Roles of Human Tryptase in the Secretary Granules of Mast Cells
| Project/Area Number |
09680624
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Single-year Grants |
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| Section | 一般 |
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| Research Field |
Functional biochemistry
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| Research Institution | The University of Tokushima |
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Principal Investigator |
SAKAI Kentaro The University of Tokushima, School of Medicine, Department of Nutrition, Research Assistant, 医学部, 助手 (60196037)
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| Co-Investigator(Kenkyū-buntansha) |
KIDO Hiroshi The University of Tokushima, Institute for Enzyme Research, Division of Enzyme Chemistry, Professor, 分子酵素科学研究センター, 教授 (50144978)
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| Project Period (FY) |
1997 – 1999
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| Project Status |
Completed (Fiscal Year 1999)
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| Budget Amount *help |
¥2,100,000 (Direct Cost: ¥2,100,000)
Fiscal Year 1999: ¥700,000 (Direct Cost: ¥700,000)
Fiscal Year 1998: ¥600,000 (Direct Cost: ¥600,000)
Fiscal Year 1997: ¥800,000 (Direct Cost: ¥800,000)
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| Keywords | Tryptase / Mast Cells / Human |
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| Research Abstract |
The human tryptase family is selectively expressed in mast cells. Products of β-tryptase gene (s) are autocatalytically processed from the pro- to the pro' enzyme at acidic pH in the presence of heparin proteoglycan, from the pro' to the mature peptide at acidic pH by dipeptidyl peptidase I, and to the enzymatically active tetramer by spontaneous conformational alterations at acidic pH in the presence of heparin. Β-Tryptase is stabilized at acidic pH by heparin, and is resistant to biologic inhibitors of serine proteases. In the absence heparin, β-tryptase spontaneously inactivates at neutral pH as it forms monomers, while at acidic pH the inactive monomers spontaneously re-form the active tetramer both in the presence and in the absence of heparin. The optimal pH for tetramer formation and reactivation is about 6, sugessting His residues play a critical role. Whether these physicochemical properties of the enzyme relate to how it is regulated in vivo is uncertain. In this regard, human β-tryptase was found to have an acidic pH optimum for cleavage of heparin proteoglycan and C3, as well as for autoprocessing. This property might restrict optimal activity in vivo to tisse or mucosal sites with an acidic pH, such as sites of inflammation and wound healing, or such as the airway. Whether reactivation of human β-tryptase occurs at extracellular or intracellular sites, where the pH is acidic in vivo, should be considered.
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Report
(4 results)
Research Products
(3 results)
