TY - JOUR
T1 - Regulation of the erythropoietin receptor and involvement of JAK2 in differentiation of J2E erythroid cells
AU - Tilbrook, Peta
AU - Bittorf, T.
AU - Callus, B.
AU - Busfield, S.J.
AU - Ingley, Evan
AU - Klinken, Peter
PY - 1996
Y1 - 1996
N2 - In response to erythropoietin, J2E cells proliferate and differentiate into mature hemoglobin-producing erythroid cells, Here we show that following hormonal stimulation, between 10 and 17 proteins, including the erythropoietin receptor and JAK2, were tyrosine phosphorylated immediately after exposure to the hormone, Although the receptor was only phosphorylated to 15% of its maximum with 0.1 unit/ml erythropoietin, this was sufficient to induce peak hemoglobin synthesis, The importance of JAK2 to J2E cell maturation was demonstrated by inhibiting JAK2 protein synthesis with antisense oligonucleotides; not only was erythropoietin-stimulated mitogenesis inhibited by this procedure, but differentiation was also suppressed, In addition, the activation of STAT5 paralleled the kinetics of receptor phosphorylation, During differentiation, 94% decrease in surface erythropoietin receptors was detected 48 h after ligand binding, but transcription of the receptor gene, mRNA steady-state levels, protein content, and translation rates did not alter with hormonal stimulation, We concluded from these experiments that (a) submaximal receptor phosphorylation is sufficient for differentiation to proceed; (b) JAK2 is required for erythropoietin-induced cell division and maturation; and (c) post-translational processing, or translocation, play important roles in controlling surface erythropoietin receptor numbers.
AB - In response to erythropoietin, J2E cells proliferate and differentiate into mature hemoglobin-producing erythroid cells, Here we show that following hormonal stimulation, between 10 and 17 proteins, including the erythropoietin receptor and JAK2, were tyrosine phosphorylated immediately after exposure to the hormone, Although the receptor was only phosphorylated to 15% of its maximum with 0.1 unit/ml erythropoietin, this was sufficient to induce peak hemoglobin synthesis, The importance of JAK2 to J2E cell maturation was demonstrated by inhibiting JAK2 protein synthesis with antisense oligonucleotides; not only was erythropoietin-stimulated mitogenesis inhibited by this procedure, but differentiation was also suppressed, In addition, the activation of STAT5 paralleled the kinetics of receptor phosphorylation, During differentiation, 94% decrease in surface erythropoietin receptors was detected 48 h after ligand binding, but transcription of the receptor gene, mRNA steady-state levels, protein content, and translation rates did not alter with hormonal stimulation, We concluded from these experiments that (a) submaximal receptor phosphorylation is sufficient for differentiation to proceed; (b) JAK2 is required for erythropoietin-induced cell division and maturation; and (c) post-translational processing, or translocation, play important roles in controlling surface erythropoietin receptor numbers.
M3 - Article
VL - 7
SP - 511
EP - 520
JO - Cell Growth & Differentiation
JF - Cell Growth & Differentiation
ER -