PMID- 22218715
OWN - NLM
STAT- MEDLINE
DCOM- 20120601
LR  - 20211021
IS  - 1791-3004 (Electronic)
IS  - 1791-2997 (Print)
IS  - 1791-2997 (Linking)
VI  - 5
IP  - 4
DP  - 2012 Apr
TI  - The JAK2-Akt-glycogen synthase kinase-3beta signaling pathway is involved in 
      toll-like receptor 2-induced monocyte chemoattractant protein-1 regulation.
PG  - 1063-7
LID - 10.3892/mmr.2012.741 [doi]
AB  - Monocyte chemoattractant protein-1 (MCP-1) is an essential cytokine for the 
      migration of monocytes into vessels, and is also involved in the pathogenesis of 
      atherosclerosis. In this study, we investigated the importance of janus kinase 2 
      (JAK2) and the function of the Akt and glycogen synthase kinase-3beta (GSK3beta) 
      pathway in toll-like receptor (TLR2)-mediated MCP-1 expression. The TLR2 agonist, 
      Pam3CSK4, induced MCP-1 expression in the Raw264.7 cell line. The induction of 
      MCP-1 was seen in the bone marrow-derived macrophages of wild-type mice but not 
      in TLR2 knockout mice. The TLR2-mediated MCP-1 induction was myeloid 
      differentiation primary response gene 88 (MyD88)-independent. By contrast, the 
      inactivation of JAK2 attenuated TLR2-mediated MCP-1 expression. The JAK inhibitor 
      suppressed the phosphorylation of GSK3beta as well as Akt by Pam3CSK4 stimulation. 
      While the inactivation of Akt by LY294002 suppressed TLR2-mediated MCP-1 
      induction, the inactivation of GSK3beta by LiCl potentiated TLR2-mediated MCP-1 
      induction. Furthermore, Akt inhibitor suppressed TLR2-mediated phosphorylation of 
      GSK3beta. Taken together, these results suggest that a MyD88-independent pathway 
      exists in TLR2 signaling; the JAK2-Akt-GSK3beta pathway is a novel MyD88-independent 
      pathway for MCP-1 induction.
FAU - Park, Dae-Weon
AU  - Park DW
AD  - Department of Biochemistry and Molecular Biology, Aging-associated Vascular 
      Disease Research Center, 210 Main Building, College of Medicine, Yeungnam 
      University, Daegu 705-802, Republic of Korea.
FAU - Lee, Hyung-Kyoung
AU  - Lee HK
FAU - Jeong, Tae-Whal
AU  - Jeong TW
FAU - Kim, Jin-Sik
AU  - Kim JS
FAU - Bae, Yoe-Sik
AU  - Bae YS
FAU - Chin, Byung-Rho
AU  - Chin BR
FAU - Baek, Suk-Hwan
AU  - Baek SH
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
DEP - 20120103
PL  - Greece
TA  - Mol Med Rep
JT  - Molecular medicine reports
JID - 101475259
RN  - 0 (Chemokine CCL2)
RN  - 0 (Chromones)
RN  - 0 (Lipopeptides)
RN  - 0 (Morpholines)
RN  - 0 (Myeloid Differentiation Factor 88)
RN  - 0 (Pam2CSK4 lipopeptide)
RN  - 0 (Toll-Like Receptor 2)
RN  - 31M2U1DVID (2-(4-morpholinyl)-8-phenyl-4H-1-benzopyran-4-one)
RN  - EC 2.7.10.2 (Janus Kinase 2)
RN  - EC 2.7.11.1 (Glycogen Synthase Kinase 3 beta)
RN  - EC 2.7.11.1 (Gsk3b protein, mouse)
RN  - EC 2.7.11.1 (Proto-Oncogene Proteins c-akt)
RN  - EC 2.7.11.26 (Glycogen Synthase Kinase 3)
RN  - G4962QA067 (Lithium Chloride)
SB  - IM
MH  - Animals
MH  - Cell Line, Tumor
MH  - Chemokine CCL2/*metabolism
MH  - Chromones/pharmacology
MH  - Glycogen Synthase Kinase 3/*metabolism
MH  - Glycogen Synthase Kinase 3 beta
MH  - Janus Kinase 2/antagonists & inhibitors/*metabolism
MH  - Lipopeptides/pharmacology
MH  - Lithium Chloride/pharmacology
MH  - Mice
MH  - Mice, Knockout
MH  - Morpholines/pharmacology
MH  - Myeloid Differentiation Factor 88/metabolism
MH  - Phosphorylation
MH  - Proto-Oncogene Proteins c-akt/*metabolism
MH  - *Signal Transduction/drug effects
MH  - Toll-Like Receptor 2/agonists/genetics/*metabolism
PMC - PMC3493083
EDAT- 2012/01/06 06:00
MHDA- 2012/06/02 06:00
PMCR- 2013/04/01
CRDT- 2012/01/06 06:00
PHST- 2011/10/17 00:00 [received]
PHST- 2011/12/21 00:00 [accepted]
PHST- 2012/01/06 06:00 [entrez]
PHST- 2012/01/06 06:00 [pubmed]
PHST- 2012/06/02 06:00 [medline]
PHST- 2013/04/01 00:00 [pmc-release]
AID - mmr-05-04-1063 [pii]
AID - 10.3892/mmr.2012.741 [doi]
PST - ppublish
SO  - Mol Med Rep. 2012 Apr;5(4):1063-7. doi: 10.3892/mmr.2012.741. Epub 2012 Jan 3.