A Morpholino oligo can modify splicing of a pre-mRNA - www.gene-tools.com



We identify Bα (PPP2R2A) and Bδ (PPP2R2D), two highly related members of the B family of regulatory subunits of the protein phosphatase PP2A, as important modulators of TGF-β/Activin/Nodal signalling that affect the pathway in opposite ways. Knockdown of Bα in Xenopus embryos or mammalian tissue culture cells suppresses TGF-β/Activin/Nodal-dependent responses, whereas knockdown of Bδ enhances these responses. Moreover, in Drosophila, overexpression of Smad2 rescues a severe wing phenotype caused by overexpression of the single Drosophila PP2A B subunit Twins. We show that, in vertebrates, Bα enhances TGF-β/Activin/Nodal signalling by stabilising the basal levels of type I receptor, whereas Bδ negatively modulates these pathways by restricting receptor activity. Thus, these highly related members of the same subfamily of PP2A regulatory subunits differentially regulate TGF-β/Activin/Nodal signalling to elicit opposing biological outcomes.


  • * These authors contributed equally to this work

  • Present address: Université de Toulouse, Centre de Biologie du Développement, CBD, UMR 5547, IFR 109, Bat 4R3, 118 route de Narbonne, 31062 Toulouse Cedex 9, France

  • Present address: High Throughput Screening Laboratory, Cancer Research UK London Research Institute, 44 Lincoln's Inn Fields, London WC2A 3PX, UK

    • Accepted July 1, 2008.
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