Distinct B subunits of PP2A regulate the NF-κB signalling pathway through dephosphorylation of IKKβ, IκBα and ReIA

PP2A is composed of a scaffolding subunit (A), a catalytic subunit (C) and a regulatory subunit (B) that is classified into four families including B, B', B '' and B '''/striatin. Here, we found that a distinct PP2A complex regulates NF-kappa B signalling by dephosphorylation of IKK beta, I kappa B alpha and RelA/p65. The PP2A core enzyme AC dimer and the holoenzyme ABC ''' trimer dephosphorylate IKK beta, I kappa B alpha and RelA, whereas the ABC trimer dephosphorylates I kappa B alpha but not IKK beta and RelA in cells. In contrast, AB'C and AB '' C trimers have little effect on dephosphorylation of these signalling proteins. These results suggest that different forms of PP2A regulate NF-kappa B pathway signalling through multiple steps each in a different manner, thereby finely tuning NF-kappa B- and IKK beta-mediated cellular responses.