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Development. September 1, 2008; 135 (17): 2927-37.

Two highly related regulatory subunits of PP2A exert opposite effects on TGF-beta/Activin/Nodal signalling.

Batut J , Schmierer B , Cao J , Raftery LA , Hill CS , Howell M .

We identify Balpha (PPP2R2A) and Bdelta (PPP2R2D), two highly related members of the B family of regulatory subunits of the protein phosphatase PP2A, as important modulators of TGF-beta/Activin/Nodal signalling that affect the pathway in opposite ways. Knockdown of Balpha in Xenopus embryos or mammalian tissue culture cells suppresses TGF-beta/Activin/Nodal-dependent responses, whereas knockdown of Bdelta 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, Balpha enhances TGF-beta/Activin/Nodal signalling by stabilising the basal levels of type I receptor, whereas Bdelta negatively modulates these pathways by restricting receptor activity. Thus, these highly related members of the same subfamily of PP2A regulatory subunits differentially regulate TGF-beta/Activin/Nodal signalling to elicit opposing biological outcomes.

PubMed ID: 18697906
Article link: Development.
Grant support: GM60501 NIGMS NIH HHS , Cancer Research UK, R01 GM060501-07 NIGMS NIH HHS , R01 GM060501-08 NIGMS NIH HHS , R01 GM060501 NIGMS NIH HHS

Genes referenced: gsc nodal odc1 ppp2r2a ppp2r2d ppp2r4 smad2 t tgfb1

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