Figure 3.

Regulation of TGF-β signalling by phosphatases. With exception of Dullard and PDP, which only act on BMP signalling, all phosphatases contribute to both pathways. PPP1 and Dullard act exclusively on receptors, whereas MTMR4, SCPs, PDP and PPM1A act exclusively on R-Smads. PPP2 can act both on receptors and R-Smads. *, PPP2 dephosphorylates the C-terminal SxS motif of Smad3 without interfering with Smad2 phosphorylation state; Dashed arrows: sequential events on TGF-β and BMP signalling pathways; Black arrows and black bars: phosphorylation or dephosphorylation events, respectively; Brown boxes: phosphatases involved; Beige boxes: PPP1 interacting proteins. PPP1, phosphoprotein phosphatase 1; PPP2, phosphoprotein phosphatase 2; PPM1A, protein phosphatase Mg²⁺/Mn²⁺ dependent 1A; PDP, pyruvate dehydrogenase phosphatase; MTMR4, myotubularin-related protein 4; SCP, small C-terminal domain phosphatase; TGF-βR, TGF-β receptor; BMPR, bone morphogenetic protein receptor; SARA, Smad anchor for receptor activation; GADD34, growth arrest and DNA damage-inducible protein 34.