Integrative signaling by minimal erythropoietin receptor forms and c-Kit.

Academic Article


  • Erythroid homeostasis depends critically upon erythropoietin (Epo) and stem cell factor cosignaling in late progenitor cells. Epo bioresponses are relayed efficiently by minimal receptor forms that retain a single Tyr-343 site for STAT5 binding, while forms that lack all cytoplasmic Tyr(P) sites activate JAK2 and the transcription of c-Myc plus presumed additional target genes. In FDCER cell lines, which express endogenous c-Kit, the signaling capacities of such minimal Epo receptor forms (ER-HY343 and ER-HY343F) have been dissected to reveal: 1) that Epo-dependent mitogenesis, survival, and bcl-x gene expression via ER-HY343 depend upon the intactness of the Tyr-343 STAT5 binding site; 2) that ER-HY343-dependent bcl-x(L) gene transcription is enhanced markedly via c-Kit; 3) that socs-3, plfap, dpp-1, and cacy-bp gene transcription is induced via ER-HY343, whereas dpp-1 and cacy-bp gene expression is also supported by ER-HY343F; 4) that ectopically expressed SOCS-3 suppresses proliferative signaling by not only ER-HY343 but also c-Kit; and 5) that in FDCER and primary erythroid cells, c-Kit appears to provide the primary route to MAPK activation. Thus, integration circuits exist in only select downstream pathways within Epo and stem call factor receptor signaling.
  • Authors

  • Pircher, TJ
  • Geiger, JN
  • Zhang, D
  • Miller, CP
  • Gaines, P
  • Wojchowski, Don
  • Status

    Publication Date

  • March 23, 2001
  • Published In


  • Base Sequence
  • Cell Division
  • Cell Line
  • Cell Survival
  • DNA Primers
  • Enzyme Activation
  • Mitogen-Activated Protein Kinases
  • Proto-Oncogene Proteins c-kit
  • Receptors, Erythropoietin
  • Signal Transduction
  • Digital Object Identifier (doi)

    Pubmed Id

  • 11124255
  • Start Page

  • 8995
  • End Page

  • 9002
  • Volume

  • 276
  • Issue

  • 12