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

Despite its wide range of known substrates, the signaling function of protein kinase CK2 is still enigmatic. Mounting evidence suggests that CK2 alpha, the catalytic subunit of holoenzymic CK2, may exist free of its usual regulatory partner CK2 beta, raising the possibility that 'free' CK2 alpha has regulation and function distinct from those of the holoenzyme. We previously reported that CK2 alpha could bind to the core dimer of protein phosphatase 2A, 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 CK2 beta are the only major substrates associating with epitope-tagged CK2 alpha, and that expression of activated Raf results in disruption of the CK2 alpha-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 CK2 alpha dose-dependently inhibits the mitogen-induced activation of cotransfected, epitope-tagged MAP kinase. We suggest that the CK2 beta free form of CK2 alpha is both a target and a regulator of Raf/MAPK signaling.