Brief Communication abstract
Nature Cell Biology 4, 963 - 969 (2002)
Published online: 11 November 2002 | doi:10.1038/ncb885
Activin/TGF-
induce apoptosis through Smad-dependent expression of the lipid phosphatase SHIP
Hector Valderrama-Carvajal1, Eftihia Cocolakis1, Annie Lacerte1, Eun-Hye Lee1, Gerald Krystal2, Suhad Ali3 & Jean-Jacques Lebrun1
Members of the transforming growth factor 
(TGF-) family regulate fundamental physiological processes, such as cell growth, differentiation and apoptosis, in almost all cell types1. As a result, defects in TGF- signalling pathways have been linked to uncontrolled cellular proliferation and carcinogenesis1. Here, we explored the signal transduction mechanisms downstream of the activin/TGF- receptors that result in cell growth arrest and apoptosis. We show that in haematopoietic cells, TGF- 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 metabolism2. We also demonstrated that the Smad pathway is required in the transcriptional regulation of the SHIP gene. Activin/TGF--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--mediated apoptosis and define TGF- family members as potent inducers of SHIP expression.
- Molecular Endocrinology Laboratory, McGill University, Department of Medicine, Royal Victoria Hospital, 687 Pine Avenue West, H3A 1A1, Montreal, Canada
- Terry Fox Laboratory, British Columbia Cancer Research Center, Vancouver, British Columbia, V5Z 1L3, Canada
- Division of Hematology, McGill University, Department of Medicine, Royal Victoria Hospital, 687 Pine Avenue West, H3A 1A1, Montreal, Canada
Correspondence to: Jean-Jacques Lebrun1 e-mail: JJ.Lebrun@MUHC.McGill.CA
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