title: Drosophila Dullard functions as a Mad phosphatase to terminate BMP signaling.
abstract: 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.
authors: Department of Biological Sciences California State University Los Angeles, 5151 State University Dr. Los Angeles, CA 90032 USA.
authors: Hugo
authors: H
authors: Urrutia
authors: Department of Biological Sciences California State University Los Angeles, 5151 State University Dr. Los Angeles, CA 90032 USA.
authors: Abigail
authors: A
authors: Aleman
authors: Department of Biological Sciences California State University Los Angeles, 5151 State University Dr. Los Angeles, CA 90032 USA.
authors: Edward
authors: E
authors: Eivers
mesh_terms: D000818:Animals; D019485:Bone Morphogenetic Proteins / Q000502:physiology*; D002460:Cell Line; D004268:DNA-Binding Proteins / Q000378:metabolism*; D029721:Drosophila Proteins / Q000378:metabolism*; D004331:Drosophila melanogaster; D060227:Imaginal Discs / Q000201:enzymology; D008297:Male; D010749:Phosphoprotein Phosphatases / Q000378:metabolism*; D010766:Phosphorylation; D011499:Protein Processing, Post-Translational; D059748:Proteolysis; D015398:Signal Transduction; D014157:Transcription Factors / Q000378:metabolism*
chemical_list: D019485:Bone Morphogenetic Proteins; D004268:DNA-Binding Proteins; D029721:Drosophila Proteins; C112506:MAD protein, Drosophila; D014157:Transcription Factors; C000627573:Dd protein, Drosophila; D010749:Phosphoprotein Phosphatases