PMID- 18181766
OWN - NLM
STAT- MEDLINE
DCOM- 20080616
LR  - 20161020
IS  - 1768-322X (Electronic)
IS  - 0248-4900 (Linking)
VI  - 100
IP  - 6
DP  - 2008 Jun
TI  - Both ERK and JNK are required for enhancement of MD-2 gene expression during 
      differentiation of HL-60 cells.
PG  - 365-75
LID - 10.1042/BC20070140 [doi]
AB  - BACKGROUND INFORMATION: MD-2 is associated with the extracellular domain of TLR4 
      (Toll-like receptor 4) and augments TLR4-dependent LPS (lipopolysaccharide) 
      responses in vitro. Our previous investigation found that PMA-induced HL-60 cell 
      differentiation to macrophages is associated largely with TLR2 and CD14 and, to a 
      much lesser extent, with TLR4. RESULTS: We studied the MD-2 expression during 
      differentiation of HL-60 cells induced by PMA. The results showed that PMA, but 
      not VitD(3) (1alpha,25-dihydroxy-vitamin D(3)), strongly induces MD-2 gene 
      expression by HL-60 cells in a time- and dose-dependent manner. Treatment with an 
      MEK [MAPK (mitogen-activated protein kinase)/ERK (extracellular-signal-regulated 
      kinase) kinase] inhibitor (PD98059) and a JNK (c-Jun N-terminal kinase) inhibitor 
      (SP600125) suppresses PMA-induced MD-2 gene expression, whereas impairment of p38 
      function by treatment with the inhibitor SB203580 has no effect on MD-2 mRNA. In 
      order to reveal the possible molecular mechanism for such a regulation of MD-2 
      gene expression, we cloned and analysed the putative MD-2 gene promoter. 
      Transient transfection of different deletion mutants demonstrated that the region 
      -185/-171 (5'-TCCTTTACAGGAAGT-3') of the MD-2 gene promoter is closely related to 
      gene transcription in response to PMA. Additionally, the transcription factor 
      Elk-1 has been found to bind this specific motif. CONCLUSIONS: These results 
      suggest that ERK and JNK pathways are involved in PMA-mediated MD-2 gene 
      expression during HL-60 cell differentiation, and the activation of the 
      MEK/possible ERK/Elk signal pathway is the mechanism responsible for PMA-induced 
      MD-2 gene expression in differentiated HL-60 cells.
FAU - Li, Changlin
AU  - Li C
AD  - Laboratory of Molecular Cell Biology, Institute of Biochemistry and Cell Biology, 
      Shanghai Institutes for Biological Sciences, Chinese Academy of Sciences, 320 Yue 
      Yang Road, Shanghai 200031, People's Republic of China.
FAU - Yu, Yongshen
AU  - Yu Y
FAU - Wang, Yun
AU  - Wang Y
FAU - Liu, Lei
AU  - Liu L
FAU - Zhang, Min
AU  - Zhang M
FAU - Sugano, Sumio
AU  - Sugano S
FAU - Wang, Zhengguo
AU  - Wang Z
FAU - Chang, Zongliang
AU  - Chang Z
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - England
TA  - Biol Cell
JT  - Biology of the cell
JID - 8108529
RN  - 0 (ELK1 protein, human)
RN  - 0 (LY96 protein, human)
RN  - 0 (Lymphocyte Antigen 96)
RN  - 0 (Protein Kinase Inhibitors)
RN  - 0 (Transcription Factors)
RN  - 0 (ets-Domain Protein Elk-1)
RN  - EC 2.7.11.24 (Extracellular Signal-Regulated MAP Kinases)
RN  - EC 2.7.11.24 (JNK Mitogen-Activated Protein Kinases)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - *Cell Differentiation/drug effects
MH  - Extracellular Signal-Regulated MAP Kinases/antagonists & inhibitors/*metabolism
MH  - *Gene Expression/drug effects
MH  - HL-60 Cells
MH  - Humans
MH  - JNK Mitogen-Activated Protein Kinases/antagonists & inhibitors/*metabolism
MH  - Lymphocyte Antigen 96/*genetics/metabolism
MH  - Promoter Regions, Genetic
MH  - Protein Kinase Inhibitors/pharmacology
MH  - Signal Transduction
MH  - Tetradecanoylphorbol Acetate/pharmacology
MH  - Transcription Factors/metabolism
MH  - ets-Domain Protein Elk-1/metabolism
EDAT- 2008/01/10 09:00
MHDA- 2008/06/17 09:00
CRDT- 2008/01/10 09:00
PHST- 2008/01/10 09:00 [pubmed]
PHST- 2008/06/17 09:00 [medline]
PHST- 2008/01/10 09:00 [entrez]
AID - BC20070140 [pii]
AID - 10.1042/BC20070140 [doi]
PST - ppublish
SO  - Biol Cell. 2008 Jun;100(6):365-75. doi: 10.1042/BC20070140.