CK2α — protein phosphatase 2A molecular complex: Possible interaction with the MAP kinase pathway

  • Franck Lebrin
  • Laurence Bianchini
  • Thierry Rabilloud
  • Edmond M. Chambaz
  • Yves Goldberg
Part of the Developments in Molecular and Cellular Biochemistry book series (DMCB, volume 27)


Despite its wide range of known substrates, the signaling function of protein kinase CK2 is still enigmatic. Mounting evidence suggests that CK2α, the catalytic subunit of holoenzymic CK2, may exist free of its usual regulatory partner CK2β, raising the possibility that ‘free’ CK2α has regulation and function distinct from those of the holoenzyme. We previously reported that CK2α could bind to the core dimer of protein phosphatase 2 A, and indirectly cause down-regulation of the PP2A substrate MEK1, possibly via activation of PP2A and/or targeting of PP2A to some element of the Ras/Raf/MEK pathway. Here, these results are confirmed and extended. By using transfection experiments and immune kinase assays, we show that endogenous PP2Ac and CK2β are the only major substrates associating with epitope-tagged CK2α, and that expression of activated Raf results in disruption of the CK2α-PP2A association. Such disruption might be a necessary step for maximal activation of the MAP kinase pathway by Raf. In keeping with this idea, overexpression of CK2α dose-dependently inhibits the mitogen-induced activation of cotransfected, epitope-tagged MAP kinase. We suggest that the CK2β free form of CK2α is both a target and a regulator of Raf/MAPK signaling. (Mol Cell Biochem 191: 207–212, 1999)

Key words

protein phosphatase 2A protein kinase CK2α MAP kinase down-regulation 


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Copyright information

© Springer Science+Business Media Dordrecht 1999

Authors and Affiliations

  • Franck Lebrin
    • 2
  • Laurence Bianchini
    • 2
  • Thierry Rabilloud
    • 1
  • Edmond M. Chambaz
    • 2
  • Yves Goldberg
    • 2
  1. 1.CEA/GrenobleDBMS-BECPGrenobleFrance
  2. 2.INSERM U244 and CEA/GrenobleDBMS-BRCEGrenobleFrance

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