Glycogen synthase kinase-3β facilitates IFN-γ-induced STAT1 activation by regulating Src homology-2 domain-containing phosphatase 2

Cheng Chieh Tsai, Jui In Kai, Wei Ching Huang, Chi Yun Wang, Yi Wang, Chia Ling Chen, Yi Ting Fang, Yee Shin Lin, Robert Anderson, Shun Hua Chen, Chiung Wen Tsao, Chiou Feng Lin

研究成果: Article同行評審

62 引文 斯高帕斯(Scopus)

摘要

Glycogen synthase kinase-3β(GSK-3β)-modulated IFN-γ-induced inflammation has been reported; however, the mechanism that activates GSK-3βand the effects of activation remain unclear. Inhibiting GSK-3β decreased IFN-γ-induced inflammation. IFN-γ treatment rapidly activated GSK-3β via neutral sphingomyelinase- and okadaic acid-sensitive phosphatase-regulated dephosphorylation at Ser9, and proline-rich tyrosine kinase 2 (Pyk2)-regulated phosphorylation at Tyr216. Pyk2 was activated through phosphatidylcholine-specific phospholipase C (PC-PLC)-, protein kinase C (PKC)-, and Src-regulated pathways. The activation of PC-PLC, Pyk2, and GSK-3β was potentially regulated by IFN-γ receptor 2-associated Jak2, but it was independent of IFN-γ receptor 1. Furthermore, Jak2/PC-PLC/PKC/cytosolic phospholipase A2 positively regulated neutral sphingomyelinase. Inhibiting GSK-3β activated Src homology-2 domain-containing phosphatase 2 (SHP2), thereby preventing STAT1 activation in the late stage of IFN-γ stimulation. All these results showed that activated GSK-3β synergistically affected IFN-γ-induced STAT1 activation by inhibiting SHP2.

原文English
頁(從 - 到)856-864
頁數9
期刊Journal of Immunology
183
發行號2
DOIs
出版狀態Published - 2009 7月 15

All Science Journal Classification (ASJC) codes

  • 免疫學和過敏
  • 免疫學

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