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

被引：57

作者：

Batut, Julie ^{[1
]}

Schmierer, Bernhard ^{[1
]}

Cao, Jing ^{[2
,3
]}

Raftery, Laurel A. ^{[2
,3
]}

Hill, Caroline S. ^{[1
]}

Howell, Michael ^{[1
]}

机构：

[1] Canc Res UK London Res Inst, Lab Dev Signalling, London WC2A 3PX, England

[2] Massachusetts Gen Hosp, Cutaneous Biol Res Ctr, Charlestown, MA 02129 USA

[3] Harvard Univ, Sch Med, Charlestown, MA 02129 USA

来源：

DEVELOPMENT | 2008年 / 135卷 / 17期

关键词：

PP2A regulatory B subunits; TGF-beta/Activin/Nodal signalling; Xenopus; Drosophila;

D O I：

10.1242/dev.020842

中图分类号：

Q [生物科学];

学科分类号：

07 ; 0710 ; 09 ;

摘要：

We identify B alpha (PPP2R2A) and B delta (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 B alpha in Xenopus embryos or mammalian tissue culture cells suppresses TGF-beta/Activin/Nodal-dependent responses, whereas knockdown of B delta 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, B alpha enhances TGF-beta/Activin/Nodal signalling by stabilising the basal levels of type I receptor, whereas B delta 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.

引用

页码：2927 / 2937

页数：11

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