Analysis of regulatory mechanism of sustained integrin alphaIIbbeta3 activation.

2016 Fiscal Year Final Research Report

• Project/Area Number: 26461403
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Hematology
• Research Institution: Osaka University
• Principal Investigator: Kato Hisashi 大阪大学, 医学系研究科, 助教 (20705214)
• Co-Investigator(Renkei-kenkyūsha): Tomiyama Yoshiaki 大阪大学, 医学部附属病院・輸血部, 准教授 (80252667)
• Research Collaborator: Ichii Michiko 大阪大学, 大学院医学系研究科・血液・腫瘍内科, 寄付講座助教 (30633010)
• Project Period (FY): 2014-04-01 – 2017-03-31
• Keywords: インテグリンαIIbβ3 / Inside-Outシグナル / CalDAG-GEFI

Outline of Final Research Achievements

Platelet fibrinogen receptor integrin αIIbβ3 is essential for hemostasis and its activation state is tightly regulated by inside-out signaling. So far, the detailed mechanism how inside-out signaling induces activation of αIIbβ3 is still obscure. In this study, we determined the molecules which are important for inside-out signaling in the megakaryocytic cell line CMK and the patient with CalDAG-GEFI deficiency who has been suffering severe bleeding problems. However, platelets with CalDAG-GEFI deficiency showed mildly impaired αIIbβ3 activation. And we found the delayed αIIbβ3 activation in CalDAG-GEFI deficient platelets is related to severe bleeding symptoms. Our results indicate the importance of CalDAG-GEFI and αIIbβ3 activation kinetics for normal hemostasis (Blood 2016).

Free Research Field

血栓止血