Identification of K-ras as the major regulator for cytokine-dependent Akt activation in erythroid progenitors in vivo
AUTOR(ES)
Zhang, Jing
FONTE
National Academy of Sciences
RESUMO
Despite intensive investigation, controversial results have been obtained concerning the precise signaling pathway(s) regulated by K-ras in different cell types. We show that in primary fetal liver erythroid progenitors, erythropoietin activates all three Ras isoforms, but preferentially N- and K-ras. In K-ras-/- fetal liver cells (FLC), erythropoietin- or stem cell factor-dependent Akt activation is greatly reduced, whereas other pathways including Stat5 and p44/p42 MAP kinase are activated normally. We further studied the effects of reduced cytokine-dependent Akt activation in erythroid differentiation. We find that freshly isolated K-ras-/- FLC show an ≈7-fold increase of apoptosis and delayed erythroid differentiation, but only at the stage of erythroid progenitors and very early erythroblasts. When K-ras-/- erythroid progenitors are cultured in vitro, there is a significant delay in erythroid differentiation but little increase in apoptosis. Furthermore, we show that partial pharmacologic inhibition of the phosphatidylinositol 3-kinase/Akt pathway in wild-type erythroid progenitors leads to a delay in erythroid differentiation similar to that observed in K-ras-/- FLC. Taken together, our data identify K-ras as the major regulator for cytokine-dependent Akt activation, which is important for erythroid differentiation in vivo.
ACESSO AO ARTIGO
http://www.pubmedcentral.nih.gov/articlerender.fcgi?artid=1253609Documentos Relacionados
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