PMID- 28754897
OWN - NLM
STAT- MEDLINE
DCOM- 20190304
LR  - 20190304
IS  - 2045-2322 (Electronic)
IS  - 2045-2322 (Linking)
VI  - 7
IP  - 1
DP  - 2017 Jul 28
TI  - Reciprocal regulation of TLR2-mediated IFN-beta production by SHP2 and Gsk3beta.
PG  - 6807
LID - 10.1038/s41598-017-07316-3 [doi]
LID - 6807
AB  - Toll-like receptor 2 (TLR2) mediates the innate immune response to bacterial 
      lipopeptides and peptidoglycans by stimulating the production of inflammatory 
      cytokines. However, the mechanisms by which TLR2 signaling regulates type I 
      interferon (IFN)-beta production are poorly understood. Here, we identified Src 
      homology 2-containing protein tyrosine phosphatase 2 (SHP2) as a negative 
      regulator of TLR2-induced IFN-beta production. Pharmacological inhibition or reduced 
      expression of SHP2 potentiated TLR2 agonist-mediated IFN-beta transcription and 
      STAT1 activation, whereas overexpression of SHP2 impaired IFN-beta transcription and 
      STAT1 activation. SHP2 physically associated with the glycogen synthase kinase 3beta 
      (Gsk3beta) in an agonist-dependent manner. Gsk3beta positively regulates transcription 
      of IFN-beta following TLR2 stimulation by inhibiting the phosphorylation of SHP2. 
      SHP2 inhibited the transcriptional activity of IRF-1 and IRF-8 at the IFN-beta 
      promoter. Remarkably, IRF-1 and IRF-8 are recruited to the IFN-beta promoter in a 
      SHP2 phosphatase activity-dependent manner. These findings provide insight into 
      the mechanisms by which SHP2 and Gsk3beta work together to modulate TLR2-mediated 
      IFN-beta production in macrophages.
FAU - Park, Jin Hee
AU  - Park JH
AD  - Department of Life Science, Ewha Womans University, Seoul, 120-750, Korea.
AD  - The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul, 
      120-750, Korea.
FAU - Ko, Ryeojin
AU  - Ko R
AD  - Department of Life Science, Ewha Womans University, Seoul, 120-750, Korea.
AD  - The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul, 
      120-750, Korea.
FAU - Lee, Soo Young
AU  - Lee SY
AD  - Department of Life Science, Ewha Womans University, Seoul, 120-750, Korea. 
      leesy@ewha.ac.kr.
AD  - The Research Center for Cellular Homeostasis, Ewha Womans University, Seoul, 
      120-750, Korea. leesy@ewha.ac.kr.
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20170728
PL  - England
TA  - Sci Rep
JT  - Scientific reports
JID - 101563288
RN  - 0 (Interferon Regulatory Factor-1)
RN  - 0 (Interferon Regulatory Factors)
RN  - 0 (Irf1 protein, mouse)
RN  - 0 (STAT1 Transcription Factor)
RN  - 0 (Tlr2 protein, mouse)
RN  - 0 (Toll-Like Receptor 2)
RN  - 0 (interferon regulatory factor-8)
RN  - 77238-31-4 (Interferon-beta)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 3.1.3.48 (Protein Tyrosine Phosphatase, Non-Receptor Type 11)
RN  - EC 3.1.3.48 (Ptpn11 protein, mouse)
SB  - IM
MH  - Animals
MH  - Cells, Cultured
MH  - Glycogen Synthase Kinase 3 beta/*metabolism
MH  - HEK293 Cells
MH  - Humans
MH  - Interferon Regulatory Factor-1/genetics/metabolism
MH  - Interferon Regulatory Factors/genetics/metabolism
MH  - Interferon-beta/genetics/*metabolism
MH  - Macrophages/metabolism
MH  - Mice
MH  - Mice, Inbred C57BL
MH  - Protein Binding
MH  - Protein Tyrosine Phosphatase, Non-Receptor Type 11/antagonists & 
      inhibitors/genetics/*metabolism
MH  - STAT1 Transcription Factor/metabolism
MH  - Toll-Like Receptor 2/genetics/*metabolism
PMC - PMC5533723
COIS- The authors declare that they have no competing interests.
EDAT- 2017/07/30 06:00
MHDA- 2019/03/05 06:00
PMCR- 2017/07/28
CRDT- 2017/07/30 06:00
PHST- 2017/03/10 00:00 [received]
PHST- 2017/06/26 00:00 [accepted]
PHST- 2017/07/30 06:00 [entrez]
PHST- 2017/07/30 06:00 [pubmed]
PHST- 2019/03/05 06:00 [medline]
PHST- 2017/07/28 00:00 [pmc-release]
AID - 10.1038/s41598-017-07316-3 [pii]
AID - 7316 [pii]
AID - 10.1038/s41598-017-07316-3 [doi]
PST - epublish
SO  - Sci Rep. 2017 Jul 28;7(1):6807. doi: 10.1038/s41598-017-07316-3.