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

Research output: Contribution to journalArticle

46 Citations (Scopus)

Abstract

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.

Original languageEnglish
Pages (from-to)856-864
Number of pages9
JournalJournal of Immunology
Volume183
Issue number2
DOIs
Publication statusPublished - Jul 15 2009

Fingerprint

SH2 Domain-Containing Protein Tyrosine Phosphatases
Glycogen Synthase Kinase 3
Focal Adhesion Kinase 2
Sphingomyelin Phosphodiesterase
Protein Kinase C
Cytosolic Phospholipases A2
Inflammation
Phosphorylation

ASJC Scopus subject areas

  • Immunology
  • Medicine(all)

Cite this

Glycogen synthase kinase-3β facilitates IFN-γ-induced STAT1 activation by regulating Src homology-2 domain-containing phosphatase 2. / Tsai, Cheng-Chieh; Kai, Jui-In; Huang, Wei-Ching; Wang, Chi-Yun; Wang, Yi; Chen, Chia-Ling; Fang, Yi-Ting; Lin, Yee-Shin; Anderson, Robert; Chen, Shun-Hua; Tsao, Chiung-Wen; Lin, Chiou Feng.

In: Journal of Immunology, Vol. 183, No. 2, 15.07.2009, p. 856-864.

Research output: Contribution to journalArticle

Tsai, C-C, Kai, J-I, Huang, W-C, Wang, C-Y, Wang, Y, Chen, C-L, Fang, Y-T, Lin, Y-S, Anderson, R, Chen, S-H, Tsao, C-W & Lin, CF 2009, 'Glycogen synthase kinase-3β facilitates IFN-γ-induced STAT1 activation by regulating Src homology-2 domain-containing phosphatase 2', Journal of Immunology, vol. 183, no. 2, pp. 856-864. https://doi.org/10.4049/jimmunol.0804033
Tsai, Cheng-Chieh ; Kai, Jui-In ; Huang, Wei-Ching ; Wang, Chi-Yun ; Wang, Yi ; Chen, Chia-Ling ; Fang, Yi-Ting ; Lin, Yee-Shin ; Anderson, Robert ; Chen, Shun-Hua ; Tsao, Chiung-Wen ; Lin, Chiou Feng. / Glycogen synthase kinase-3β facilitates IFN-γ-induced STAT1 activation by regulating Src homology-2 domain-containing phosphatase 2. In: Journal of Immunology. 2009 ; Vol. 183, No. 2. pp. 856-864.
@article{e148761f271548c28011247931cb02ed,
title = "Glycogen synthase kinase-3β facilitates IFN-γ-induced STAT1 activation by regulating Src homology-2 domain-containing phosphatase 2",
abstract = "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.",
author = "Cheng-Chieh Tsai and Jui-In Kai and Wei-Ching Huang and Chi-Yun Wang and Yi Wang and Chia-Ling Chen and Yi-Ting Fang and Yee-Shin Lin and Robert Anderson and Shun-Hua Chen and Chiung-Wen Tsao and Lin, {Chiou Feng}",
year = "2009",
month = "7",
day = "15",
doi = "10.4049/jimmunol.0804033",
language = "English",
volume = "183",
pages = "856--864",
journal = "Journal of Immunology",
issn = "0022-1767",
publisher = "American Association of Immunologists",
number = "2",

}

TY - JOUR

T1 - Glycogen synthase kinase-3β facilitates IFN-γ-induced STAT1 activation by regulating Src homology-2 domain-containing phosphatase 2

AU - Tsai, Cheng-Chieh

AU - Kai, Jui-In

AU - Huang, Wei-Ching

AU - Wang, Chi-Yun

AU - Wang, Yi

AU - Chen, Chia-Ling

AU - Fang, Yi-Ting

AU - Lin, Yee-Shin

AU - Anderson, Robert

AU - Chen, Shun-Hua

AU - Tsao, Chiung-Wen

AU - Lin, Chiou Feng

PY - 2009/7/15

Y1 - 2009/7/15

N2 - 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.

AB - 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.

UR - http://www.scopus.com/inward/record.url?scp=70249114863&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=70249114863&partnerID=8YFLogxK

U2 - 10.4049/jimmunol.0804033

DO - 10.4049/jimmunol.0804033

M3 - Article

VL - 183

SP - 856

EP - 864

JO - Journal of Immunology

JF - Journal of Immunology

SN - 0022-1767

IS - 2

ER -