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Erythropoietin induces Raf-1 activation and Raf-1 is required for erythropoietin-mediated proliferation
Ist Teil von
The Journal of biological chemistry, 1991-08, Vol.266 (23), p.14964-14969
Ort / Verlag
Bethesda, MD: American Society for Biochemistry and Molecular Biology
Erscheinungsjahr
1991
Quelle
MEDLINE
Beschreibungen/Notizen
Erythropoietin mediates the rapid phosphorylation of Raf-1 in the murine cell lines HCD-57 and FDC-P1/ER, which proliferate
in response to this cytokine. Phosphorylation occurs at both serine and tyrosine residues and as such is similar to the Raf-1
phosphorylation seen after interleukin-3 (IL-3), granulocyte-macrophage colony-stimulating factor, and interleukin-2 stimulation
in other murine cell lines. Such data suggest that these growth factors may share a common mechanism(s) of Raf-1 phosphorylation.
Furthermore, in association with Raf-1 phosphorylation, erythropoietin induces a 2-3-fold increase in Raf-1 kinase activity
as measured in immune complex kinase assays in vitro. Finally, a c-raf antisense oligodeoxyribonucleotide, which specifically
decreases intracellular Raf-1 levels, also substantially inhibits both erythropoietin and IL-3-directed DNA synthesis. Together,
these results provide evidence that activated Raf-1 is a necessary component of erythropoietin and IL-3 growth signaling pathways.