ABSENCE OF CYTOKINE RECEPTOR-DEPENDENT SPECIFICITY IN RED-BLOOD-CELL DIFFERENTIATION IN-VIVO

Erythropoietin (EPO) is required for red blood cell development, hut w hether EPO-specific signals directly instruct erythroid differentiatio n is unknown. We used a dominant system in which constitutively active variants of the EPO receptor were introduced into erythroid progenito rs in mice. Chimeric receptors were constructed by replacing the cytop lasmic tail of constitutively active variants of the EPO receptor with tails of diverse cytokine receptors. Receptors linked to granulocyte or platelet production supported complete erythroid development in vit ro and in vivo, as did the growth hormone receptor, a nonhematopoietic receptor. Therefore, EPOR-specific signals are not required for termi nal differentiation of erythrocytes. Furthermore, we found that cellul ar context can influence cytokine receptor signaling.