Protein Phosphatase 2, Regulatory Subunit B Delta (PPP2R2d)

PP2A is a multimeric serine/threonine protein phosphatase consisting of a 36 kDa catalytic subunit (PP2AC) and a 65 kDa scaffolding subunit. PPP2R2A and PPP2R2D have distinct and opposing roles in the regulation of TGF-β/Activin/Nodal signalling. Smad2 association with the homeodomain transcription factor goosecoid, the C2-WW-HECT ubiquitin ligase, WWP2, and the protein phosphatase 2 regulatory subunit, PPP2R2D, as well as interactions between Smad4 and either Map kinase kinase 3 (MAP2K3) or TC21 (RRAS2). The identification of WWP2, extends the range of C2-WW-HECT ubiquitin ligases that function in Smad signaling beyond the Smurf subfamily and the presence of PPP2R2D suggests one potential mechanism for turning off Smad signaling by dephosphorylation. Overexpressed PPP2R2D was found to inhibit TGFβ-dependent Smad signaling .