Biol Cell 2004,
PMID: 15380617
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.
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Text Mining Data
Dashed line = No text mining data
Manually curated Databases
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IRef Biogrid Interaction:
PPP2R5E
—
CHEK2
(direct interaction, pull down)
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IRef Biogrid Interaction:
PPP2R5E
—
CHEK2
(direct interaction, two hybrid)
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IRef Biogrid Interaction:
PPP2R5A
—
CHEK2
(direct interaction, pull down)
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IRef Biogrid Interaction:
PPP2R5A
—
CHEK2
(direct interaction, two hybrid)
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IRef Biogrid Interaction:
CHEK2
—
PPP2R5D
(direct interaction, two hybrid)
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IRef Biogrid Interaction:
CHEK2
—
PPP2R5D
(direct interaction, pull down)
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IRef Biogrid Interaction:
PPP2R1A
—
PPP2R5C
(physical association, affinity chromatography technology)
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IRef Biogrid Interaction:
PPP2R5B
—
CHEK2
(direct interaction, pull down)
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IRef Biogrid Interaction:
PPP2R2B
—
CHEK2
(direct interaction, two hybrid)
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IRef Biogrid Interaction:
PPP2R1A
—
CHEK2
(physical association, affinity chromatography technology)
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IRef Biogrid Interaction:
PPP2CA
—
CHEK2
(physical association, affinity chromatography technology)
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IRef Biogrid Interaction:
MBP
—
PPP2R5C
(direct interaction, enzymatic study)
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IRef Biogrid Interaction:
CHEK2
—
PPP2R5C
(direct interaction, two hybrid)
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IRef Biogrid Interaction:
CHEK2
—
PPP2R5C
(direct interaction, pull down)
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IRef Biogrid Interaction:
CHEK2
—
PPP2R5C
(physical association, affinity chromatography technology)
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IRef Biogrid Interaction:
CHEK2
—
PPP2R5C
(direct interaction, enzymatic study)
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IRef Biogrid Interaction:
PPP2CA
—
PPP2R5C
(physical association, affinity chromatography technology)
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IRef Hprd Interaction:
PPP2R5E
—
CHEK2
(in vitro)
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IRef Hprd Interaction:
PPP2R5E
—
CHEK2
(two hybrid)
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IRef Hprd Interaction:
PPP2R5A
—
CHEK2
(two hybrid)
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IRef Hprd Interaction:
PPP2R5A
—
CHEK2
(in vivo)
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IRef Hprd Interaction:
PPP2R5A
—
CHEK2
(in vitro)
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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)
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IRef Hprd Interaction:
MAPK1
—
HLA-DRA
(in vitro)
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IRef Hprd Interaction:
CHEK2
—
PPP2R5C
(in vitro)
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IRef Hprd Interaction:
CHEK2
—
PPP2R5C
(two hybrid)
-
IRef Hprd Interaction:
CHEK2
—
PPP2R5C
(in vivo)
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IRef Hprd Interaction:
PPP2R2A
—
CHEK2
(in vitro)
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IRef Hprd Interaction:
PPP2R2A
—
CHEK2
(in vivo)
-
IRef Hprd Interaction:
PPP2R2A
—
CHEK2
(two hybrid)
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IRef Intact Interaction:
CHEK2
—
PPP2R5E
(physical association, pull down)
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IRef Intact Interaction:
CHEK2
—
PPP2R5E
(physical association, two hybrid)
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IRef Intact Interaction:
PPP2R5A
—
CHEK2
(physical association, two hybrid)
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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