TGF-β/Activin/Nodal signalling regulates many developmental processes and is itself regulated in a highly complex fashion. Now, Batut and co-workers unexpectedly reveal that two closely related regulatory subunits of the serine/threonine protein phosphatase PP2A - Bα and Bδ - modulate TGF-β/Activin/Nodal signalling in opposite ways (see ). TGF-β/Activin/Nodal ligands bind to type II serine/threonine receptor kinases, which phosphorylate and activate type I receptor kinases. These phosphorylate receptor-regulated Smads, which form complexes with Smad4 that affect development by regulating target gene expression. The researchers show that Bα knockdown in Xenopus embryos and in mammalian cells in culture suppresses TGF-β/Activin/Nodal-dependent responses, but that Bδ knockdown enhances these responses. Other experiments indicate that Bα enhances TGF-β/Activin/Nodal signalling by stabilizing type I receptor basal levels, whereas Bδ reduces signalling by restricting receptor activity. Thus, suggest the researchers, the ratio of Bα to Bδ in a cell will influence its threshold response to TGF-β/Activin/Nodal ligands and consequently determine its subsequent behaviour.
