Gene interactions and pathways from curated databases and text-mining
Biol Cell 2004, PMID: 15380617

Regulation of Chk2 phosphorylation by interaction with protein phosphatase 2A via its B' regulatory subunit.

Dozier, Christine; Bonyadi, Mortaza; Baricault, Laurent; Tonasso, Laure; Darbon, Jean-Marie

Chk2 is a key player of the DNA damage signalling pathway. To identify new regulators of this kinase, we performed a yeast two-hybrid screen and found that Chk2 associated with the B' regulatory subunit of protein phosphatase PP2A. In vitro GST-Chk2 pulldowns demonstrated that B'gamma isoforms bound to Chk2 with the strongest apparent affinity. This was confirmed in cellulo by co-immunoprecipitation after overexpression of the respective partners in HEK293 cells. The A and C subunits of PP2A were present in the complexes, suggesting that Chk2 was associated with a functionnal PP2A. In vitro kinase assays showed that B'gamma3 was a potent Chk2 substrate. This phosphorylation increased the catalytic phosphatase activity of PP2A measured on MAP kinase-phosphorylated myelin basic protein as well as on autophosphorylated Chk2. Finally, we demonstrated that overexpressing B'gamma3 in HEK293 suppressed the phosphorylation of Chk2 induced by a genotoxic treatment, suggesting that PP2A may counteract the action of the checkpoint kinase in living cells.

Document information provided by NCBI PubMed

Text Mining Data

Dashed line = No text mining data

Manually curated Databases

  • IRef Biogrid Interaction: PPP2R5E — CHEK2 (direct interaction, pull down)
  • IRef Biogrid Interaction: PPP2R5E — CHEK2 (direct interaction, two hybrid)
  • IRef Biogrid Interaction: PPP2R5A — CHEK2 (direct interaction, pull down)
  • IRef Biogrid Interaction: PPP2R5A — CHEK2 (direct interaction, two hybrid)
  • IRef Biogrid Interaction: CHEK2 — PPP2R5D (direct interaction, two hybrid)
  • IRef Biogrid Interaction: CHEK2 — PPP2R5D (direct interaction, pull down)
  • IRef Biogrid Interaction: PPP2R1A — PPP2R5C (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: PPP2R5B — CHEK2 (direct interaction, pull down)
  • IRef Biogrid Interaction: PPP2R2B — CHEK2 (direct interaction, two hybrid)
  • IRef Biogrid Interaction: PPP2R1A — CHEK2 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: PPP2CA — CHEK2 (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: MBP — PPP2R5C (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: CHEK2 — PPP2R5C (direct interaction, two hybrid)
  • IRef Biogrid Interaction: CHEK2 — PPP2R5C (direct interaction, pull down)
  • IRef Biogrid Interaction: CHEK2 — PPP2R5C (physical association, affinity chromatography technology)
  • IRef Biogrid Interaction: CHEK2 — PPP2R5C (direct interaction, enzymatic study)
  • IRef Biogrid Interaction: PPP2CA — PPP2R5C (physical association, affinity chromatography technology)
  • IRef Hprd Interaction: PPP2R5E — CHEK2 (in vitro)
  • IRef Hprd Interaction: PPP2R5E — CHEK2 (two hybrid)
  • IRef Hprd Interaction: PPP2R5A — CHEK2 (two hybrid)
  • IRef Hprd Interaction: PPP2R5A — CHEK2 (in vivo)
  • IRef Hprd Interaction: PPP2R5A — CHEK2 (in vitro)
  • IRef Hprd Interaction: PPP2R5D — CHEK2 (in vitro)
  • IRef Hprd Interaction: PPP2R5D — CHEK2 (two hybrid)
  • IRef Hprd Interaction: PPP2R5B — CHEK2 (in vivo)
  • IRef Hprd Interaction: PPP2R5B — CHEK2 (two hybrid)
  • IRef Hprd Interaction: PPP2R5B — CHEK2 (in vitro)
  • IRef Hprd Interaction: MAPK1 — HLA-DRA (in vitro)
  • IRef Hprd Interaction: CHEK2 — PPP2R5C (in vitro)
  • IRef Hprd Interaction: CHEK2 — PPP2R5C (two hybrid)
  • IRef Hprd Interaction: CHEK2 — PPP2R5C (in vivo)
  • IRef Hprd Interaction: PPP2R2A — CHEK2 (in vitro)
  • IRef Hprd Interaction: PPP2R2A — CHEK2 (in vivo)
  • IRef Hprd Interaction: PPP2R2A — CHEK2 (two hybrid)
  • IRef Intact Interaction: CHEK2 — PPP2R5E (physical association, pull down)
  • IRef Intact Interaction: CHEK2 — PPP2R5E (physical association, two hybrid)
  • IRef Intact Interaction: PPP2R5A — CHEK2 (physical association, two hybrid)
  • IRef Intact Interaction: PPP2R5A — CHEK2 (physical association, pull down)
  • IRef Intact Interaction: CHEK2 — PPP2R5D (physical association, two hybrid)
  • IRef Intact Interaction: CHEK2 — PPP2R5B (physical association, pull down)
  • IRef Intact Interaction: CHEK2 — PPP2R5B (physical association, two hybrid)
  • IRef Intact Interaction: PPP2R5C — CHEK2 (physical association, pull down)
  • IRef Intact Interaction: CHEK2 — PPP2R5C (physical association, two hybrid)
  • IRef Intact Interaction: PPP2R5C — CHEK2 (physical association, two hybrid)
  • IRef Intact Interaction: CHEK2 — PPP2R5C (physical association, pull down)
  • IRef Intact Interaction: CHEK2 — PPP2R5C (physical association, anti tag coimmunoprecipitation)
  • IRef Intact Interaction: CHEK2 — PPP2R5C (phosphorylation reaction, protein kinase assay)
In total, 13 gene pairs are associated to this article in curated databases