TY - JOUR
T1 - CCAAT/enhancer binding protein ε
T2 - Changes in function upon phosphorylation by p38 MAP kinase
AU - Williamson, Elizabeth A.
AU - Williamson, Ian K.
AU - Chumakov, Alexey M.
AU - Friedman, Alan D.
AU - Koeffler, H. Phillip
PY - 2005/5/15
Y1 - 2005/5/15
N2 - C/EBPε, a member of the CCAAT/enhancer binding protein family, is a transcription factor important in neutrophil differentiation. We have determined that it is phosphorylated on multiple serine and threonine residues and can be a target for phosphorylation by a number of kinases. We identified a threonine at amino acid 75, part of a consensus mitogen-activated protein (MAP) kinase site within the transactivation domain of C/EBPε, as being phosphorylated only by p38 MAP kinase. Phosphorylation of this residue resulted in enhanced transcriptional activity on a myeloid-specific promoter in in vitro transient transfection reporter assays. We also determined that phosphorylation at Thr75 yielded a protein that was more effective at binding its cognate DNA sequence compared with the wild-type nonphosphorylated C/EBPε. Stable expression of C/EBPεT75A in interleukin 3 (IL-3)-dependent 32Dc13 did not result in the up-regulation of expression of secondary granule genes compared with wild-type C/EBPε or C/EBPεT75D. Therefore we suggest that C/EBPε is a target for p38 MAP kinase activity.
AB - C/EBPε, a member of the CCAAT/enhancer binding protein family, is a transcription factor important in neutrophil differentiation. We have determined that it is phosphorylated on multiple serine and threonine residues and can be a target for phosphorylation by a number of kinases. We identified a threonine at amino acid 75, part of a consensus mitogen-activated protein (MAP) kinase site within the transactivation domain of C/EBPε, as being phosphorylated only by p38 MAP kinase. Phosphorylation of this residue resulted in enhanced transcriptional activity on a myeloid-specific promoter in in vitro transient transfection reporter assays. We also determined that phosphorylation at Thr75 yielded a protein that was more effective at binding its cognate DNA sequence compared with the wild-type nonphosphorylated C/EBPε. Stable expression of C/EBPεT75A in interleukin 3 (IL-3)-dependent 32Dc13 did not result in the up-regulation of expression of secondary granule genes compared with wild-type C/EBPε or C/EBPεT75D. Therefore we suggest that C/EBPε is a target for p38 MAP kinase activity.
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U2 - 10.1182/blood-2004-09-3708
DO - 10.1182/blood-2004-09-3708
M3 - Article
C2 - 15677566
AN - SCOPUS:18544381583
SN - 0006-4971
VL - 105
SP - 3841
EP - 3847
JO - Blood
JF - Blood
IS - 10
ER -