PMID- 14729073
OWN - NLM
STAT- MEDLINE
DCOM- 20040224
LR  - 20190610
IS  - 0006-3002 (Print)
IS  - 0006-3002 (Linking)
VI  - 1635
IP  - 2-3
DP  - 2003 Dec 30
TI  - Regulation of sphingosine kinase 1 gene expression by protein kinase C in a human 
      leukemia cell line, MEG-O1.
PG  - 104-16
AB  - The prolonged treatment with phorbol 12-myristate 13-acetate (PMA) of a human 
      megakaryoblastic leukemia cell line, MEG-O1, induced increase of sphingosine 
      kinase (SPHK) enzyme activity and SPHK1 protein expression as well as SPHK1 
      message. Protein kinase C (PKC) inhibitor prevented the PMA-induced SPHK1 gene 
      expression. To elucidate the regulatory mechanism of this gene expression, we 
      examined the promoter area (distal to the first exon) and its binding proteins. 
      Luciferase analyses showed that the area of 300 bp from the first exon was 
      sufficient for PMA-responsiveness, and that specificity protein 1 (Sp1)- and two 
      activator protein 2 (AP-2)-binding motifs within this area were necessary for 
      responsiveness. Inhibitors for PKC and MEK1 decreased this PMA-induced promoter 
      activity. Electrophoresis mobility shift assay (EMSA) showed that Sp1 protein was 
      originally bound to the Sp1 site and that two additional bands bound to the two 
      AP-2 motifs were observed only when stimulated with PMA in MEG-O1 cells. The 
      appearance of these bands resulted from binding to an unknown protein rather than 
      AP-2. These results indicated that PMA up-regulates SPHK1 gene expression through 
      PMA-responsive elements of the 5' promoter area of the gene, and suggested that 
      PMA-mediated SPHK1 gene expression would be mediated via PKC- and ERK-dependent 
      signal transduction pathway by binding the transcription factor to AP-2 motifs.
FAU - Nakade, Yusuke
AU  - Nakade Y
AD  - Nagoya University Graduate School of Medicine, Nagoya University School of Health 
      Sciences, Higashi, Japan.
FAU - Banno, Yoshiko
AU  - Banno Y
FAU - T-Koizumi, Keiko
AU  - T-Koizumi K
FAU - Hagiwara, Kazumi
AU  - Hagiwara K
FAU - Sobue, Sayaka
AU  - Sobue S
FAU - Koda, Masahiro
AU  - Koda M
FAU - Suzuki, Motoshi
AU  - Suzuki M
FAU - Kojima, Tetsuhito
AU  - Kojima T
FAU - Takagi, Akira
AU  - Takagi A
FAU - Asano, Haruhiko
AU  - Asano H
FAU - Nozawa, Yoshinori
AU  - Nozawa Y
FAU - Murate, Takashi
AU  - Murate T
LA  - eng
PT  - Journal Article
PT  - Research Support, Non-U.S. Gov't
PL  - Netherlands
TA  - Biochim Biophys Acta
JT  - Biochimica et biophysica acta
JID - 0217513
RN  - 0 (DNA-Binding Proteins)
RN  - 0 (Oligonucleotide Probes)
RN  - 0 (Sp1 Transcription Factor)
RN  - 0 (Transcription Factor AP-2)
RN  - 0 (Transcription Factors)
RN  - EC 2.7.1.- (Phosphotransferases (Alcohol Group Acceptor))
RN  - EC 2.7.1.- (sphingosine kinase)
RN  - EC 2.7.11.13 (Protein Kinase C)
RN  - EC 2.7.11.24 (Mitogen-Activated Protein Kinases)
RN  - NI40JAQ945 (Tetradecanoylphorbol Acetate)
SB  - IM
MH  - Binding Sites
MH  - Cell Line, Tumor
MH  - DNA-Binding Proteins/metabolism
MH  - Electrophoretic Mobility Shift Assay
MH  - *Gene Expression Regulation, Enzymologic/drug effects
MH  - Humans
MH  - Leukemia
MH  - Mitogen-Activated Protein Kinases/physiology
MH  - Oligonucleotide Probes
MH  - Phosphotransferases (Alcohol Group Acceptor)/biosynthesis/genetics/*metabolism
MH  - Promoter Regions, Genetic/physiology
MH  - Protein Kinase C/*physiology
MH  - Signal Transduction
MH  - Sp1 Transcription Factor/metabolism
MH  - Tetradecanoylphorbol Acetate
MH  - Transcription Factor AP-2
MH  - Transcription Factors/metabolism
MH  - Transcription, Genetic
EDAT- 2004/01/20 05:00
MHDA- 2004/02/26 05:00
CRDT- 2004/01/20 05:00
PHST- 2004/01/20 05:00 [pubmed]
PHST- 2004/02/26 05:00 [medline]
PHST- 2004/01/20 05:00 [entrez]
AID - S1388198103001720 [pii]
AID - 10.1016/j.bbalip.2003.11.001 [doi]
PST - ppublish
SO  - Biochim Biophys Acta. 2003 Dec 30;1635(2-3):104-16. doi: 
      10.1016/j.bbalip.2003.11.001.