The envelope protein of SFFV interacts with the EpoR and sf-Stk to activate signal transduction pathways for growth, differentiation and survival of erythroid cells. (A) SFFV Env interacts with the EpoR, causing phosphorylation of the adaptor molecules IRS-2 and Gab1/2. This leads to activation of the Ras/Raf/MAPK and PI3-K pathways and phosphorylation of Stats 1 and 5, resulting in Epo-independent proliferation, differentiation and survival. (B) Covalent interaction of SFFV Env with sf-Stk results in activation of Grb2, Gab2 and Stat3. This leads to activation of the Ras/Raf/MAPK and PI-3K pathways and Epo-independent erythroid cell proliferation and survival. P = phosphorylation event; S-S = disulfide bond.