Abstract
Smad2 and Smad3 (Smad2/3) are essential signal transducers and transcription factors in the canonical transforming growth factor-β (TGF-β) signalling pathway. Active Smad2/3 signalling in the nucleus is terminated by dephosphorylation and subsequent nuclear export of Smad2/3. Here we report that protein phosphatase PPM1A regulates the nuclear export of Smad2/3 through targeting nuclear exporter RanBP3. PPM1A directly interacted with and dephosphorylated RanBP3 at Ser 58 in vitro and in vivo. Consistently, RanBP3 phosphorylation was elevated in PPM1A-null mouse embryonic fibroblasts. Dephosphorylation of RanBP3 at Ser 58 promoted its ability to export Smad2/3 and terminate TGF-β responses. Our findings indicate the critical role of PPM1A in maximizing exporter activity of RanBP3 for efficient termination of canonical TGF-β signalling.
Original language | English (US) |
---|---|
Pages (from-to) | 1175-1181 |
Number of pages | 7 |
Journal | EMBO reports |
Volume | 12 |
Issue number | 11 |
DOIs | |
State | Published - Nov 2011 |
Keywords
- PP2Ca
- Smads
- TGF-β signalling
- phosphorylation
- termination
ASJC Scopus subject areas
- Biochemistry
- Molecular Biology
- Genetics