Title

Identification of phosphatases for Smad in the BMP/DPP pathway

UMMS Affiliation

Program in Molecular Medicine; Department of Cancer Biology

Date

3-3-2006

Document Type

Article

Subjects

Animals; Base Sequence; Bone Morphogenetic Proteins; DNA Primers; Drosophila; Drosophila Proteins; Phosphorylation; Polymerase Chain Reaction; Pyruvate Dehydrogenase (Lipoamide)-Phosphatase; Signal Transduction; Smad Proteins; Subcellular Fractions

Disciplines

Life Sciences | Medicine and Health Sciences

Abstract

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.

Rights and Permissions

Citation: Genes Dev. 2006 Mar 15;20(6):648-53. Epub 2006 Mar 1. Link to article on publisher's site

DOI of Published Version

10.1101/gad.1384706

Related Resources

Link to Article in PubMed

Journal Title

Genes and development

PubMed ID

16510868