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The distal cytoplasmic domain of the erythropoietin receptor induces granulocytic differentiation in 32D cells.

Publication ,  Journal Article
Harris, KW; Hu, XJ; Schultz, S; Arcasoy, MO; Forget, BG; Clare, N
Published in: Blood
August 15, 1998

The role of hematopoietic growth factors in lineage commitment and differentiation is unclear. We present evidence that heterologous expression of an erythroid specific receptor allows granulocytic differentiation of a myeloid cell line. We have previously characterized a truncation mutant of the erythropoietin receptor (EpoR), which is associated with familial erythrocytosis (Blood 89:4628, 1997). This truncated EpoR lacks the distal 70 amino acids of the cytoplasmic domain. To study the functional role of this distal receptor domain, 32D cells, a murine interleukin-3 (IL-3)-dependent myeloid line, were transfected with the wild-type EpoR (32D/EpoR WT) or the truncated EpoR (32D/EpoR FE). 32D cells expressing either the full-length or truncated EpoR display equivalent proliferative rates in saturating concentrations of Epo. There is a dramatic difference in maturational phenotype between the two cell lines, however. The 32D/EpoR FE cells and mock transfected 32D cells have an immature, monoblastic morphology and do not express the primary granule protein myeloperoxidase. The 32D/EpoR WT cells, on the other hand, demonstrate granulocytic differentiation with profuse granulation, mature, clumped chromatin, and myeloperoxidase expression. There is no evidence of erythroid differentiation in 32D cells transfected with either the full-length or truncated EpoR. Treatment of the cells with the specific Jak2 inhibitor tyrphostin AG 490 inhibits myeloid differentiation driven by the distal EpoR. We conclude that: (1) the distal cytoplasmic domain of the EpoR is able to induce a specific myeloid differentiation signal distinct from mitogenic signaling, and (2) these data extend to myelopoiesis the growing body of evidence that the cellular milieu, not the specific cytokine receptor, determines the specificity of differentiation after cytokine receptor activation.

Duke Scholars

Published In

Blood

ISSN

0006-4971

Publication Date

August 15, 1998

Volume

92

Issue

4

Start / End Page

1219 / 1224

Location

United States

Related Subject Headings

  • Tyrphostins
  • Transfection
  • Structure-Activity Relationship
  • Signal Transduction
  • Recombinant Fusion Proteins
  • Receptors, Erythropoietin
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • Protein Structure, Tertiary
  • Polycythemia
 

Citation

APA
Chicago
ICMJE
MLA
NLM
Harris, K. W., Hu, X. J., Schultz, S., Arcasoy, M. O., Forget, B. G., & Clare, N. (1998). The distal cytoplasmic domain of the erythropoietin receptor induces granulocytic differentiation in 32D cells. Blood, 92(4), 1219–1224.
Harris, K. W., X. J. Hu, S. Schultz, M. O. Arcasoy, B. G. Forget, and N. Clare. “The distal cytoplasmic domain of the erythropoietin receptor induces granulocytic differentiation in 32D cells.Blood 92, no. 4 (August 15, 1998): 1219–24.
Harris KW, Hu XJ, Schultz S, Arcasoy MO, Forget BG, Clare N. The distal cytoplasmic domain of the erythropoietin receptor induces granulocytic differentiation in 32D cells. Blood. 1998 Aug 15;92(4):1219–24.
Harris, K. W., et al. “The distal cytoplasmic domain of the erythropoietin receptor induces granulocytic differentiation in 32D cells.Blood, vol. 92, no. 4, Aug. 1998, pp. 1219–24.
Harris KW, Hu XJ, Schultz S, Arcasoy MO, Forget BG, Clare N. The distal cytoplasmic domain of the erythropoietin receptor induces granulocytic differentiation in 32D cells. Blood. 1998 Aug 15;92(4):1219–1224.

Published In

Blood

ISSN

0006-4971

Publication Date

August 15, 1998

Volume

92

Issue

4

Start / End Page

1219 / 1224

Location

United States

Related Subject Headings

  • Tyrphostins
  • Transfection
  • Structure-Activity Relationship
  • Signal Transduction
  • Recombinant Fusion Proteins
  • Receptors, Erythropoietin
  • Proto-Oncogene Proteins
  • Protein-Tyrosine Kinases
  • Protein Structure, Tertiary
  • Polycythemia