Abstract
The immature erythroid J2E cell line proliferates and terminally differentiates following erythropoietin stimulation. In contrast, the mutant J2E-NR clone does not respond to erythropoietin by either proliferating or differentiating. Here we show that erythropoietin can act as a viability factor for both the J2E and J2E-NR lines, indicating that erythropoietin-initiated maturation is separable from the prevention of cell death. The inability of J2E-NR cells to mature in response to erythropoietin was not due to a defect in the erythropoietin receptor sequence, although surface receptor numbers were reduced. Both the receptor and Janus kinase 2 were phosphorylated after erythropoietin stimulation of J2E-NR cells. However, protein interactions with the erythropoietin receptor and Grb2 were restricted in the mutant cells. Subsequent investigation of several other signaling molecules exposed numerous alterations in J2E-NR cells; phosphorylation changes to phosphatidylinositol 3-kinase, phospholipase Cgamma, p120 GAP, and mitogen-activated protein kinases (p42 and p44) observed in erythropoietin-stimulated J2E cells were not seen in the J2E-NR line. These data indicate that some pathways activated during erythropoietin-induced differentiation may not be essential for the prevention of apoptosis.
Highlights
Erythropoietin (Epo)1 is the principal regulator of red blood cell development, which acts primarily on immature erythroid precursors to maintain cell viability and promote proliferation and terminal differentiation [1,2,3]
Since Epo inhibits the death of J2E-NR cells and the mitogen-activated protein (MAP) kinase pathway was not activated by the hormone, we suggest that this pathway is not involved in maintaining the viability of these cells
We show here that Epo still has an effect on the J2E-NR cells by supporting viability in the absence of serum
Summary
Erythropoietin (Epo)1 is the principal regulator of red blood cell development, which acts primarily on immature erythroid precursors to maintain cell viability and promote proliferation and terminal differentiation [1,2,3]. Subsequent investigation of several other signaling molecules exposed numerous alterations in J2E-NR cells; phosphorylation changes to phosphatidylinositol 3-kinase, phospholipase C␥, p120 GAP, and mitogen-activated protein kinases (p42 and p44) observed in erythropoietin-stimulated J2E cells were not seen in the J2E-NR line.
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