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Article Dans Une Revue Biology of the Cell Année : 2004

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

Résumé

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.

Dates et versions

hal-00317533 , version 1 (03-09-2008)

Identifiants

Citer

Christine Dozier, Mortaza Bonyadi, Laurent Baricault, Laure Tonasso, Jean-Marie Darbon. Regulation of Chk2 phosphorylation by interaction with protein phosphatase 2A via its B' regulatory subunit.. Biology of the Cell, 2004, 96 (7), pp.509-17. ⟨10.1016/j.biolcel.2004.04.010⟩. ⟨hal-00317533⟩
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