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PP2A regulates BMP signalling by interacting with BMP receptor complexes and by dephosphorylating both the C-terminus and the linker region of Smad1
Luiza Bengtsson, Raphaela Schwappacher, Martin Roth, Jan H. Boergermann, Sylke Hassel, Petra Knaus


Phosphorylation of Smads is a crucial regulatory step in the signal transduction pathway initiated by bone morphogenetic proteins (BMPs). Although the dephosphorylation events terminating the pathway in the nucleus have been characterized, little is known about the dephosphorylation of Smads in the cytoplasm. In a proteomic screen for proteins interacting with the BMP type-II receptor, we found the regulatory Bβ subunit of PP2A. PP2A is one of the major serine/threonine phosphatases involved in cell-cycle regulation and signal transduction. Here, we present data showing that the Bβ subunit of PP2A interacts with both BMP type-I and type-II receptors. Furthermore, we demonstrate that several B subunits can associate with the BMP type-II receptor, independently of the kinase activity of the receptor and the catalytic subunit of PP2A. By contrast, the PP2A catalytic subunit is required for PP2A function at the receptor complex. This function of PP2A is the dephosphorylation of Smad1, mainly in the linker region. PP2A-mediated dephosphorylation of the BMP-Smad linker region leads to increased nuclear translocation of Smads and overall amplification of the BMP signal. Although other phosphatases identified within the BMP pathway are all shown to inhibit signalling, PP2A is the first example for a signalling stimulatory phosphatase within this pathway.


  • Supplementary material available online at

  • We thank Sabrina Scholz (University of Wuerzburg, Wuerzburg, Germany), Verena Ezerski, Cathleen Rohleder, Sonja Niedrig and the students from the practical course `signal transduction' (Carmen Borck, Laura Jaenicke, Seon-Hi Jang, York Posor, Karin Schlegelmilch and Mario Stephan) from the practical course “signal transduction” (FU Berlin, Berlin, Germany) for excellent technical assistance. We are also grateful to Thomas J. Jentsch for his support. This work was supported by the German Research Foundation Collaborative Research Centre SFB 760 (P.K.) and the FU Berlin Research Council (L.B.).

  • * These authors contributed equally to this work

  • Present address: MDC/FMP, Robert Roessle Strasse 10, 13125 Berlin, Germany

  • § Present address: Faculty of Life Sciences, University of Manchester, Oxford Road, Manchester M13 9PT, UK

  • Accepted December 27, 2008.
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