Activation of the Akt/FKHRL1 pathway mediates the antiapoptotic effects of erythropoietin in primary human erythroid progenitors

Shahab Uddin*, Samanthi Kottegoda, Danielle Stigger, Leonidas C. Platanias, Amittha Wickrema

*Corresponding author for this work

Research output: Contribution to journalArticlepeer-review

84 Scopus citations

Abstract

Erythropoietin (Epo), stem cell factor (SCF), and insulin-like growth factor-1 (IGF-1) are key regulators of erythroid cell proliferation and differentiation. To understand the mechanisms of generation of signals by each of these growth factors, we determined the activation of the PI3-kinase/Akt pathway during proliferation and differentiation of primary human erythroid progenitors. Our results demonstrate that Pt(B/Akt is activated by Epo and SCF, but not by IGF-1 in human primary erythroid progenitors. In addition, Epo treatment of erythroid progenitors induces phosphorylation of a member of the Forkhead family (FH) of transcription factors FKHRL1, downstream of actiration of the Akt kinase. Such Epo-dependent activation of FKHRL1 apparently regulates the generation of Epo-dependent antiapoptotic signals as evidenced by the induction of apoptosis of erythrold progenitors during treatment of cells with the PI3-kinase (PI3K) inhibitor LY294002. Thus, the PI3K/Akt/FKHRL1 pathway is essential for inhibition of apoptosis in response to Epo and SCF, while the IGF-1 receptor utilizes a different pathway. (C) 2000 Academic Press.

Original languageEnglish (US)
Pages (from-to)16-19
Number of pages4
JournalBiochemical and Biophysical Research Communications
Volume275
Issue number1
DOIs
StatePublished - Aug 18 2000

ASJC Scopus subject areas

  • Biophysics
  • Biochemistry
  • Molecular Biology
  • Cell Biology

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