Gene interactions and pathways from curated databases and text-mining
J Biol Chem 2002, PMID: 11839738

Protein kinase C-delta (PKC-delta ) is activated by type I interferons and mediates phosphorylation of Stat1 on serine 727.

Uddin, Shahab; Sassano, Antonella; Deb, Dilip K; Verma, Amit; Majchrzak, Beata; Rahman, Arshad; Malik, Asrar B; Fish, Eleanor N; Platanias, Leonidas C

It is well established that engagement of the Type I interferon (IFN) receptor results in activation of JAKs (Janus kinases), which in turn regulate tyrosine phosphorylation of STAT proteins. Subsequently, the IFN-dependent tyrosine-phosphorylated/activated STATs translocate to the nucleus to regulate gene transcription. In addition to tyrosine phosphorylation, phosphorylation of Stat1 on serine 727 is essential for induction of its transcriptional activity, but the IFNalpha-dependent serine kinase that regulates such phosphorylation remains unknown. In the present study we provide evidence that PKC-delta, a member of the protein kinase C family of proteins, is activated during engagement of the Type I IFN receptor and associates with Stat1. Such an activation of PKC-delta appears to be critical for phosphorylation of Stat1 on serine 727, as inhibition of PKC-delta activation diminishes the IFNalpha- or IFNbeta-dependent serine phosphorylation of Stat1. In addition, treatment of cells with the PKC-delta inhibitor rottlerin or the expression of a dominant-negative PKC-delta mutant results in inhibition of IFNalpha- and IFNbeta-dependent gene transcription via ISRE or GAS elements. Interestingly, PKC-delta inhibition also blocks activation of the p38 MAP kinase, the function of which is required for IFNalpha-dependent transcriptional regulation, suggesting a dual mechanism by which this kinase participates in the generation of IFNalpha responses. Altogether, these findings indicate that PKC-delta functions as a serine kinase for Stat1 and an upstream regulator of the p38 MAP kinase and plays an important role in the induction of Type I IFN-biological responses.

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Text Mining Data

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Manually curated Databases

  • OpenBEL Selventa BEL large corpus: STAT1 → PRKCD (increases, PRKCD Activity, STAT1 Activity)
    Evidence: Modified assertion
  • OpenBEL Selventa BEL large corpus: STAT1 → PRKCD (directlyIncreases, STAT1 Activity)
    Evidence: In the present study we provide evidence that PKC-delta, a member of the protein kinase C family of proteins, is activated during engagement of the Type I IFN receptor and associates with Stat1. Such an activation of PKC-delta appears to be critical for phosphorylation of Stat1 on serine 727, as inhibition of PKC-delta activation diminishes the IFNalpha- or IFNbeta-dependent serine phosphorylation of Stat1.
  • IRef Biogrid Interaction: ATF2 — MAPK14 (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: PRKCD — STAT1 (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: PRKCD — STAT1 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: PRKCD — HIST1H1B (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: MAPKAPK2 — HSPB1 (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: PRKCD — PRKCD (direct interaction, enzymatic study)
  • IRef Hprd Interaction: LCK — STAT1 (in vitro)
  • IRef Hprd Interaction: LCK — STAT1 (in vivo)
  • IRef Hprd Interaction: STAT1 — JAK1 (in vivo)
  • IRef Hprd Interaction: STAT1 — JAK1 (in vitro)
  • IRef Hprd Interaction: FGFR3 — STAT1 (in vivo)
  • IRef Hprd Interaction: FGFR3 — STAT1 (in vitro)
  • IRef Hprd Interaction: STAT1 — PRKCD (in vitro)
  • IRef Hprd Interaction: STAT1 — PRKCD (in vivo)
  • IRef Hprd Interaction: STAT1 — PRKCD (two hybrid)
  • IRef Hprd Interaction: STAT1 — EGFR (in vitro)
  • IRef Hprd Interaction: STAT1 — EGFR (in vivo)
  • IRef Hprd Interaction: TYK2 — STAT1 (in vivo)
  • IRef Hprd Interaction: TYK2 — STAT1 (in vitro)
  • IRef Hprd Interaction: FGFR4 — STAT1 (in vitro)
  • IRef Hprd Interaction: FGFR4 — STAT1 (in vivo)
  • IRef Hprd Interaction: STAT1 — CAMK2G (in vivo)
  • IRef Hprd Interaction: STAT1 — CAMK2G (in vitro)
  • IRef Hprd Interaction: STAT1 — JAK2 (in vivo)
  • IRef Hprd Interaction: STAT1 — JAK2 (in vitro)
In total, 13 gene pairs are associated to this article in curated databases