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Published online before print March 1, 2006, 10.1101/gad.1384706
GENES & DEVELOPMENT 20:648-653, 2006
©2006 by Cold Spring Harbor Laboratory Press; ISSN 0890-9369/ $5.00
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RESEARCH COMMUNICATION

Identification of phosphatases for Smad in the BMP/DPP pathway

Hong B. Chen, Jiali Shen, Y. Tony Ip and Lan Xu1

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 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.

[Keywords: Bone morphogenetic protein; Decapentaplegic; Mothers against Decapentaplegic; Smad; pyruvate dehydrogenase phosphatase]

Received October 14, 2005; revised version accepted January 13, 2006.


1 Corresponding author.

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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