2016 Fiscal Year Final Research Report
Research for the regulation of factor VIII by activated protein C and protein S
| Project/Area Number |
26461592
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| Research Category |
Grant-in-Aid for Scientific Research (C)
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| Allocation Type | Multi-year Fund |
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| Section | 一般 |
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| Research Field |
Pediatrics
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| Research Institution | Nara Medical University |
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Principal Investigator |
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| Project Period (FY) |
2014-04-01 – 2017-03-31
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| Keywords | 第VIII因子 / 血友病 / 活性型プロテインC / プロテインS / 第IX因子 / 第X因子 |
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| Outline of Final Research Achievements |
Factor (F) VIII functions as a cofactor in the tenase complex responsible for phospholipid (PL) surface-dependent conversion of FX to FXa by FIXa. On the other hand, protein S (PS) functions as a cofactor of activated protein C that inactivates FVIII(a) and FV(a). We have reported a new regulatory mechanism on coagulation that PS directly impaired the FXase complex by competing the FIXa-FVIIIa interaction (Takeyama, Br J Haematol. 2008 Nov;143(3):409-20), and identified the PS-interactive site on the FVIII A2 domain. However, the contribution of FVIII light chain (LC) to PS-binding has not been determined. In this study, several approaches were employed to assess a PS-FVIII LC interaction. In conclusion, FVIII C2 domain, in particular K2239, was possible to play an important role of the inhibitory mechanism to FVIII function by PS, due to the binding to PS.
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| Free Research Field |
血液凝固
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