Bone morphogenetic proteins (BMPs) are growth factors that provide essential signals for normal embryonic development and adult tissue homeostasis. A key step in initiating BMP signaling is ligand induced phosphorylation of receptor Smads (R-Smads) by type I receptor kinases, while linker phosphorylation of R-Smads has been shown to cause BMP signal termination. Here we present data demonstrating that the phosphatase Dullard is involved in dephosphorylating the Drosophila R-Smad, Mad, and is integral in controlling BMP signal duration. We show that a hypomorphic Dullard allele or Dullard knockdown leads to increased Mad phosphorylation levels, while Dullard overexpression resulted in reduced Mad phosphorylations. Co-immunoprecipitation binding assays demonstrate phosphorylated Mad and Dullard physically interact, while mutation of Dullard’s phosphatase domain still allowed Mad-Dullard interactions but abolished its ability to regulate Mad phosphorylations. Finally, we demonstrate that linker and C-terminally phosphorylated Mad can be regulated by one of two terminating mechanisms, degradation by proteasomes or dephosphorylation by the phosphatase Dullard.

Scientific Reports 6: Article number: 32269; published online: 31 August 2016; updated: 22 December 2017. This Article contains errors in Figure 4, where the blot for pMadS212 in panel 4c was unintentionally swapped with the pMadCter blot from panel 4d. In addition, Figure S2 in the original versionof the Supplementary Information was incorrect, where the blots for Flag-Mad-AVA were unintentionally swapped between panels S2c and S2d.