We found a match
Your institution may have rights to this item. Sign in to continue.
- Title
Activin/TGF-β induce apoptosis through Smad-dependent expression of the lipid phosphatase SHIP.
- Authors
Valderrama-Carvajal, Hector; Cocolakis, Eftihia; Lacerte, Annie; Lee, Eun-Hye; Krystal, Gerald; Ali, Suhad; Lebrun, Jean-Jacques
- Abstract
Members of the transforming growth factor β (TGF-β) family regulate fundamental physiological processes, such as cell growth, differentiation and apoptosis, in almost all cell types. As a result, defects in TGF-β signalling pathways have been linked to uncontrolled cellular proliferation and carcinogenesis. Here, we explored the signal transduction mechanisms downstream of the activin/TGF-β receptors that result in cell growth arrest and apoptosis. We show that in haematopoietic cells, TGF-β family members regulate apoptosis through expression of the inositol phosphatase SHIP (Src homology 2 (SH2) domain-containing 5 inositol phosphatase), a central regulator of phospholipid metabolism. We also demonstrated that the Smad pathway is required in the transcriptional regulation of the SHIP gene. Activin/TGF-β-induced expression of SHIP results in intracellular changes in the pool of phospholipids, as well as in inhibition of both Akt/PKB (protein kinase B) phosphorylation and cell survival. Our results link phospholipid metabolism to activin/TGF-β-mediated apoptosis and define TGF-β family members as potent inducers of SHIP expression.
- Subjects
TRANSFORMING growth factors-beta; ACTIVIN
- Publication
Nature Cell Biology, 2002, Vol 4, Issue 12, p963
- ISSN
1465-7392
- Publication type
Article
- DOI
10.1038/ncb885