Imperial College London
Alternate

DrWeiCui

Faculty of Medicine, Department of Metabolism, Digestion and Reproduction

Senior Lecturer
 
 
 
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Contact

 

+44 (0)20 7594 2124wei.cui Website

 
 
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Location

 

1010Institute of Reproductive and Developmental BiologyHammersmith Campus

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Summary

 

Publications

Citation

BibTex format

@article{Yu:2015:10.1038/ncomms8212,
author = {Yu, JS and Ramasamy, TS and Murphy, N and Holt, MK and Czapiewski, R and Wei, SK and Cui, W},
doi = {10.1038/ncomms8212},
journal = {Nature Communications},
title = {PI3K/mTORC2 regulates TGF-β/Activin signalling by modulating Smad2/3 activity via linker phosphorylation},
url = {http://dx.doi.org/10.1038/ncomms8212},
volume = {6},
year = {2015}
}
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RIS format (EndNote, RefMan)

TY  - JOUR
AB  - Crosstalk between the phosphatidylinositol 3-kinase (PI3K) and the transforming growth factor-β signalling pathways play an important role in regulating many cellular functions. However, the molecular mechanisms underpinning this crosstalk remain unclear. Here, we report that PI3K signalling antagonizes the Activin-induced definitive endoderm (DE) differentiation of human embryonic stem cells by attenuating the duration of Smad2/3 activation via the mechanistic target of rapamycin complex 2 (mTORC2). Activation of mTORC2 regulates the phosphorylation of the Smad2/3-T220/T179 linker residue independent of Akt, CDK and Erk activity. This phosphorylation primes receptor-activated Smad2/3 for recruitment of the E3 ubiquitin ligase Nedd4L, which in turn leads to their degradation. Inhibition of PI3K/mTORC2 reduces this phosphorylation and increases the duration of Smad2/3 activity, promoting a more robust mesendoderm and endoderm differentiation. These findings present a new and direct crosstalk mechanism between these two pathways in which mTORC2 functions as a novel and critical mediator.
AU  - Yu,JS
AU  - Ramasamy,TS
AU  - Murphy,N
AU  - Holt,MK
AU  - Czapiewski,R
AU  - Wei,SK
AU  - Cui,W
DO  - 10.1038/ncomms8212
PY  - 2015///
SN  - 2041-1723
TI  - PI3K/mTORC2 regulates TGF-β/Activin signalling by modulating Smad2/3 activity via linker phosphorylation
T2  - Nature Communications
UR  - http://dx.doi.org/10.1038/ncomms8212
UR  - http://hdl.handle.net/10044/1/23306
VL  - 6
ER  -
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