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RESEARCH COMMUNICATION
Program in Molecular Medicine, University of Massachusetts Medical School, Worcester, Massachusetts 01605, USA
Phosphorylation of the SSXS motif of Smads is critical in activating the transforming growth factor 
(TGF-) 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--activated Smad2 or Smad3. Thus, PDPs specifically inactivate Smads in the BMP/DPP pathway.
[Keywords: Bone morphogenetic protein; Decapentaplegic; Mothers against Decapentaplegic; Smad; pyruvate dehydrogenase phosphatase]
Received October 14, 2005; revised version accepted January 13, 2006.
E-MAIL lan.xu{at}umassmed.edu; FAX (508) 856-6662.
Article published online ahead of print. Article and publication date are at http://www.genesdev.org/cgi/doi/10.1101/gad.1384706
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