Diacylglycerol kinase alpha enhances protein kinase Czeta-dependent phosphorylation at Ser311 of p65/RelA subunit of nuclear factor-kappaB.
We recently reported that diacylglycerol kinase (DGK) alpha enhanced tumor necrosis factor-alpha (TNF-alpha)-induced activation of nuclear factor-kappaB (NF-kappaB). However, the signaling pathway between DGKalpha and NF-kappaB remains unclear. Here, we found that small interfering RNA-mediated knockdown of DGKalpha strongly attenuated protein kinase C (PKC) zeta-dependent phosphorylation of a large subunit of NF-kappaB, p65/RelA, at Ser311 but not PKCzeta-independent phosphorylation at Ser468 or Ser536. Moreover, knockdown and overexpression of PKCzeta suppressed and synergistically enhanced DGKalpha-mediated NF-kappaB activation, respectively. These results strongly suggest that DGKalpha positively regulates TNF-alpha-dependent NF-kappaB activation via the PKCzeta-mediated Ser311 phosphorylation of p65/RelA.
Kai
Masahiro
M
Department of Biochemistry, Sapporo Medical University School of Medicine, Sapporo, Japan.
Yasuda
Satoshi
S
Imai
Shin-ichi
S
Toyota
Minoru
M
Kanoh
Hideo
H
Sakane
Fumio
F
D019852:Diacylglycerol Kinase / Q000235:genetics / Q000378:metabolism*; D006801:Humans; D020672:I-kappa B Proteins / Q000378:metabolism; D010766:Phosphorylation; D011493:Protein Kinase C / Q000378:metabolism*; D034622:RNA Interference; D012694:Serine / Q000378:metabolism*; D051996:Transcription Factor RelA / Q000378:metabolism*; D000099221:Protein Kinase C zeta
D019852:Diacylglycerol Kinase; D020672:I-kappa B Proteins; D011493:Protein Kinase C; D012694:Serine; D051996:Transcription Factor RelA; D000099221:Protein Kinase C zeta; C083487:I kappa B beta protein; C498143:RELA protein, human