RhoA downstream of G(q) and G(12/13) pathways regulates protease-activated receptor-mediated dense granule release in platelets.
RhoA downstream of G(q) and G(12/13) pathways regulates protease-activated receptor-mediated dense granule release in platelets.
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DOI：
10.1016/j.bcp.2008.11.017
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发表时间：
2009-03-01
影响因子：
5.8
通讯作者：
Kunapuli, Satya P.
中科院分区：
文献类型：
--
作者：
Jin, Jianguo;Mao, Yingying;Thomas, Dafydd;Kim, Soochong;Daniel, James L.;Kunapuli, Satya P.
血小板分泌是止血过程中的重要生理事件。除了Gq途径外，蛋白酶激活受体PAR 1和PAR 4以及血栓烷受体还激活G12/13途径。在这里，我们研究了G12/13途径对血小板致密颗粒释放的贡献。2 MeSADP不激活G12/13通路，在阿司匹林处理的血小板中不引起致密颗粒释放。然而，用YFLLRNP（60 μM）作为G12/13途径的选择性激活剂补充2 MeSADP，导致致密颗粒释放。类似地，用G12/13刺激补充PLC活化也导致致密颗粒释放。这些结果表明，Gq介导的致密颗粒释放需要来自G12/13的补充信号，并且ADP不能引起致密颗粒释放，因为血小板P2 Y受体虽然激活PLC，但不激活G12/13途径。当G12/13通路的下游信号分子RhoA被阻断时，PAR介导的致密颗粒释放被抑制。此外，ADP激活Rho A下游的Gq和上游的PLC。最后，Rho A调节PKCδ T505磷酸化，表明Rho A通路通过PKCδ活化促进血小板分泌。我们的结论是，G12/13途径，通过RhoA，调节致密颗粒释放和纤维蛋白原受体激活血小板。
Platelet secretion is an important physiological event in hemostasis. The protease activated receptors, PAR 1 and PAR 4, and the thromboxane receptor activate the G12/13 pathways, in addition to the Gq pathways. Here, we investigated the contribution of G12/13 pathways to platelet dense granule release. 2MeSADP, which does not activate G12/13 pathways, does not cause dense granule release in aspirin-treated platelets. However, supplementing 2MeSADP with YFLLRNP (60 μM), as selective activator of G12/13 pathways, resulted in dense granule release. Similarly, supplementing PLC activation with G12/13 stimulation also leads to dense granule release. These results demonstrate that supplemental signaling from G12/13 is required for Gq-mediated dense granule release and that ADP fails to cause dense granule release because the platelet P2Y receptors, although activate PLC, do not activate G12/13 pathways. When RhoA, downstream signaling molecule in G12/13 pathways, is blocked, PAR-mediated dense granule release is inhibited. Furthermore, ADP activated Rho A downstream of Gq and upstream of PLC. Finally, Rho A regulated PKCδ T505 phosphorylation, suggesting that Rho A pathways contribute to platelet secretion through PKCδ activation. We conclude that G12/13 pathways, through RhoA, regulate dense granule release and fibrinogen receptor activation in platelets.
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DOI：
10.1111/j.1365-2362.1994.tb02418.x
发表时间：
1994-02-01
影响因子：
5.5
作者：
HOLMSEN, H
通讯作者：
HOLMSEN, H
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作者：
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DOI：
10.1073/pnas.94.16.8750
发表时间：
1997-08-05
影响因子：
11.1
作者：
Gabbeta, J;Yang, X;Rao, AK
通讯作者：
Rao, AK
影响因子：
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作者：
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