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Sci Rep. 2016 Aug 31;6:32269. doi: 10.1038/srep32269.

Drosophila Dullard functions as a Mad phosphatase to terminate BMP signaling.

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Department of Biological Sciences California State University Los Angeles, 5151 State University Dr. Los Angeles, CA 90032 USA.


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.

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