Analysis of signal transduction in glycolipid microdomains

2017 Fiscal Year Final Research Report

• Project/Area Number: 26440071
• Research Category: Grant-in-Aid for Scientific Research (C)
• Allocation Type: Multi-year Fund
• Section: 一般
• Research Field: Functional biochemistry
• Research Institution: Tokyo Metropolitan Institute of Medical Science
• Principal Investigator: KASAHARA Kohji 公益財団法人東京都医学総合研究所, 生体分子先端研究分野, 副室長 (60250213)
• Project Period (FY): 2014-04-01 – 2018-03-31
• Keywords: 脂質ラフト / 糖脂質ミクロドメイン / シグナル伝達

Outline of Final Research Achievements

SDF-1α-induced platelet aggregation is mediated through its G protein-coupled receptor CXCR4 and PI3K. Here, we demonstrate that SDF-1α induces phosphorylation of Akt at Thr308 and Ser473 in platelets. SDF-1α-induced platelet aggregation and Akt phosphorylation are inhibited by the CXCR4 antagonist AMD3100 or the PI3K inhibitor LY294002. SDF-1α-induced platelet aggregation is inhibited by pretreatment with the Akt inhibitor MK-2206 in a dose-dependent manner. Furthermore,SDF-1α-induced platelet aggregation and Akt phosphorylation are inhibited by pretreatment with the raft-disrupting agent methyl-β-cyclodextrin. Sucrose density gradient analysis shows that 35% of CXCR4, 93% of the heterotrimeric G proteins Gαi-1, 91% of Gαi-2, 50% of Gβ and 4.0% of PI3Kβ, and 4.5% of Akt2 are localized in the detergent-resistant membrane raft fraction. These findings suggest that SDF-1α/CXCR4 signaling in lipid rafts induces platelet aggregation via PI3K-dependent Akt phosphorylation.

Free Research Field

生化学