Identification of phosphatases for Smad in the BMP/DPP pathway.
Phosphorylation of the SSXS motif of Smads is critical in activating the transforming growth factor beta (TGF-beta) and bone morphogenetic protein (BMP) pathways. However, the phosphatase(s) involved in dephosphorylating and hence inactivating Smads remained elusive. Through RNA interference (RNAi)-based screening of serine/threonine phosphatases in Drosophila S2 cells, we identified pyruvate dehydrogenase phosphatase (PDP) to be required for dephosphorylation of Mothers against Decapentaplegic (MAD), a Drosophila Smad. Biochemical and genetic evidence suggest that PDP directly dephosphorylates MAD and inhibits signal transduction of Decapentaplegic (DPP). We show that the mammalian PDPs are important in dephosphorylation of BMP-activated Smad1 but not TGF-beta-activated Smad2 or Smad3. Thus, PDPs specifically inactivate Smads in the BMP/DPP pathway.
Chen
Hong B
HB
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA.
Shen
Jiali
J
Ip
Y Tony
YT
Xu
Lan
L
D000818:Animals; D001483:Base Sequence; D019485:Bone Morphogenetic Proteins / Q000378:metabolism*; D017931:DNA Primers; D004330:Drosophila; D029721:Drosophila Proteins / Q000378:metabolism*; D010766:Phosphorylation; D016133:Polymerase Chain Reaction; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase / Q000378:metabolism*; D015398:Signal Transduction; D051785:Smad Proteins / Q000378:metabolism*; D013347:Subcellular Fractions / Q000201:enzymology
D019485:Bone Morphogenetic Proteins; D017931:DNA Primers; D029721:Drosophila Proteins; D051785:Smad Proteins; C064196:dpp protein, Drosophila; D011769:Pyruvate Dehydrogenase (Lipoamide)-Phosphatase