Erythropoiesis requires erythropoietin (Epo) and stem cell factor (SCF) signaling via their receptors EpoR and c-Kit. EpoR ¿ like many other receptors involved in hematopoiesis¿ acts via the kinase Jak2. Deletion of EpoR or Jak2 causes embryonic lethality due to defective erythropoiesis. The contribution of distinct EpoR/Jak2-induced signaling pathways (MAPK, PI3K, Stat5) to functional erythropoiesis is incompletely understood. Here we demonstrate that expression of a constitutively activated Stat5a mutant (cS5) was sufficient to relieve the proliferation defect of Jak2-/- and EpoR-/- cells in an Epo-independent manner. Also tamoxifen-induced DNA binding of a Stat5a-ER* fusion construct enabled erythropoiesis in the absence of Epo. Furthermore, c-Kit could enhance signaling through the Jak2-Stat5 axis, particularly in lymphoid and myeloid progenitors. Although abundance of hematopoietic stem cells was 2.5-fold reduced in Jak2-/- fetal livers, transplantation of Jak2-/--cS5 fetal liver cells into irradiated mice gave rise to mature erythroid and myeloid cells of donor origin up to 6 months after transplantation. Cytokine- and c-Kit pathways do not function independently of each other in hematopoiesis, but cooperate to attain full Jak2/Stat5 activation. In conclusion, activated Stat5 is a critical downstream effector of Jak2 in erythro-/myelopoiesis, and Jak2 functionally links cytokine- with c-Kit-receptor tyrosine kinase signaling.