| First Author | Zhang J | Year | 2005 |
| Journal | Proc Natl Acad Sci U S A | Volume | 102 |
| Issue | 41 | Pages | 14605-10 |
| PubMed ID | 16203968 | Mgi Jnum | J:102491 |
| Mgi Id | MGI:3607660 | Doi | 10.1073/pnas.0507446102 |
| Citation | Zhang J, et al. (2005) Identification of K-ras as the major regulator for cytokine-dependent Akt activation in erythroid progenitors in vivo. Proc Natl Acad Sci U S A 102(41):14605-10 |
| abstractText | 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 approximately 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. |
