期刊
BLOOD
卷 105, 期 7, 页码 2749-2756出版社
AMER SOC HEMATOLOGY
DOI: 10.1182/blood-2004-07-2821
关键词
-
类别
资金
- NHLBI NIH HHS [T32 HL07777, HL60683, HL64943] Funding Source: Medline
G(12/13) or G(q) signaling pathways activate platelet GPIIb/IIIa when combined with G(i) signaling. We tested whether combined G(i) and G(z) pathways also cause GPIIb/IIIa activation and compared the signaling requirements of these events. Platelet aggregation occurred by combined stimulation of G(i) and G, pathways in human platelets and in P2Y(1)-deficient and G alpha(q)-deficient mouse platelets, confirming that the combination of G(i) and G(z) signaling causes platelet aggregation. When G(i) stimulation was combined with G(z) stimulation, there was a small mobilization of intracellular calcium. Chelation of intracellular calcium decreased the extent of this platelet aggregation, whereas it abolished the G(q) plus G(i)-mediated platelet aggregation. Costimulation of G(i) plus G(z) pathways also caused thromboxane generation that was dependent on outside-in signaling and was inhibited by PP2, a Src family tyrosine kinase inhibitor. Src family tyrosine kinase inhibitors also inhibited platelet aggregation and decreased the PAC-1 binding caused by costimulation of G(i) and G(z) signaling pathways in aspirin-treated platelets. However, Src family kinase inhibitors did not affect G(q) plus G(i)-mediated platelet aggregation. We conclude that the combination of Gi plus Gz pathways have different requirements than G(q) plus G(i) pathways for calcium and Src family kinases in GPIIb/IIIa activation and thromboxane production.
作者
我是这篇论文的作者
点击您的名字以认领此论文并将其添加到您的个人资料中。
推荐
暂无数据