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

Wan-Jung Lu, Kao Chang Lin, Shih Yi Huang, Philip Aloysius Thomas, Yu Hua Wu, Hsu Chu Wu, Kuan Hung Lin, Joen Rong Sheu

Research output: Contribution to journalArticle

25 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)1088-1096
Number of pages9
JournalThrombosis Research
Volume133
Issue number6
DOIs
Publication statusPublished - 2014

Keywords

  • AG490
  • JAK2
  • JNK
  • PKC
  • Platelet activation

ASJC Scopus subject areas

  • Hematology
  • Medicine(all)

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