Erythropoietin activates Raf1 by an Shc-independent pathway in CTLL-EPO-R cells

Stimulation of the erythropoietin receptor (EPO-R) or the interleukin-a receptor (IL-2-R) by their respective ligands has been reported to activate tyrosine phosphorylation of the cytoplasmic protein, She. We have recently characterized a cell line, CTLL-EPO-R, that contains functional cell-surface receptors for both EPO and IL-2. Although stimulation with IL-2 or IL-15 resulted in the rapid, dose-dependent tyrosine phosphorylation of She, stimulation with EPO failed to activate She. EPO, IL-2, and IL-15 activated the tyrosine phosphorylation of the adaptor protein, Shp2, and the association of Shp2/Grh2/cytokine receptor complexes. in addition, EPO, IL-2, and IL-15 activated Raf1 and ERK2, demonstrating that the Raf1/MEK/MAP kinase pathway was activated. These results indicate that multiple biochemical pathways are capable of conferring a mitogenic signal in CTLL-EPO-R. EPO can activate the Raf1/MEK/MAP kinase pathway via She-dependent or She-independent pathways, and She activation is not required for EPO-dependent cell growth in CTLL-EPO-R. (C) 1997 by The American Society of Hematology.