Diacylglycerol kinase α enhances protein kinase Cζ‐dependent phosphorylation at Ser311 of p65/RelA subunit of nuclear factor‐κB

We recently reported that diacylglycerol kinase (DGK) α enhanced tumor necrosis factor‐α (TNF‐α)‐induced activation of nuclear factor‐κB (NF‐κB). However, the signaling pathway between DGKα and NF‐κB remains unclear. Here, we found that small interfering RNA‐mediated knockdown of DGKα strongly attenuated protein kinase C (PKC) ζ‐dependent phosphorylation of a large subunit of NF‐κB, p65/RelA, at Ser311 but not PKCζ‐independent phosphorylation at Ser468 or Ser536. Moreover, knockdown and overexpression of PKCζ suppressed and synergistically enhanced DGKα‐mediated NF‐κB activation, respectively. These results strongly suggest that DGKα positively regulates TNF‐α‐dependent NF‐κB activation via the PKCζ‐mediated Ser311 phosphorylation of p65/RelA.