Role of a Janus kinase 2-dependent signaling pathway in platelet activation

請使用永久網址來引用或連結此文件: http://140.112.115.32:8080/ir/handle/987654321/2782

題名:	Role of a Janus kinase 2-dependent signaling pathway in platelet activation
作者:	Wan-Jung Lu, Kao-Chang Lin, Shih-Yi Huang, Philip Aloysius Thomas, Yu-Hua Wu, Hsu-Chu Wu, Kuan-Hung Lin, Joen-Rong Sheu
貢獻者:	視光學系
關鍵詞:	AG490;JAK2;Platelet activation;PKC;JNK
日期:	2014-06-01
上傳時間:	2025-08-01 15:07:11 (UTC+8)
摘要:	Introduction Janus kinases (JAKs) are intracellular non-receptor tyrosine kinases that transduce cytokine-mediated signals through a pathway mediated by JAK and the signal transducer and activator of transcription (STAT) proteins. The JAK-STAT pathway is involved in immune response, inflammation, and tumorigenesis. Platelets are anuclear blood cells that play a central role in hemostasis. Methods The aggregometry, immunoblotting, and platelet functional analysis used in this study. Results We found that the JAK2 inhibitor AG490 (25 and 50 μM) attenuated collagen-induced platelet aggregation and calcium mobilization in a concentration-dependent manner. In the presence of AG490, the phosphorylation of PLCγ2, protein kinase C (PKC), Akt or JNK in collagen-activated aggregation of human platelets was also inhibited. In addition, we found that various inhibitors, such as the PLCγ2 inhibitor U73122, the PKC inhibitor Ro318220, the phospoinositide 3-kinase inhibitor LY294002, the p38 mitogen-activated protein kinase inhibitor SB203580, the ERK inhibitor PD98059, and the JNK inhibitor SP600125, had no effects on collagen-induced JAK2 activity. However, U73122, Ro318220 and SP600125 significantly diminished collagen-induced STAT3 phosphorylation. These findings suggest that PLCγ2-PKC and JNK are involved in JAK2-STAT3 signaling in collagen-activated platelets. Conclusion Our results demonstrate that the JAK2-STAT3 pathway is involved in collagen-induced platelet activation through the activation of JAK2-JNK/PKC-STAT3 signaling. The inhibition of JAK2 may represent a potential therapeutic strategy for the preventing or treating thromboembolic disorders.
關聯:	Thrombosis Research, 133(6), 1088-1096. https://doi.org/10.1016/j.thromres.2014.03.042
顯示於類別:	[視光學系] 期刊論文

文件中的檔案:

檔案	大小	格式	瀏覽次數
index.html	0Kb	HTML	17	檢視/開啟

在MMUIR中所有的資料項目都受到原著作權保護.

資料載入中.....