The box1 domain of the erythropoietin receptor specifies Janus kinase 2 activation and functions mitogenically within an interleukin 2 beta-receptor chimera.

Academic Article


  • Several distinct classes of cytokine receptors engage Jak kinases as primary effectors. Among type 1 receptors, Janus-activated kinase (Jak) recruitment is mediated by membrane-proximal cytoplasmic domains, which typically contain conserved box motifs. In the erythropoietin receptor (Epo-R), two such motifs (box1 and box2) have been suggested to be essential for the activation of Jak2 and mitogenesis. Presently, an Epo-R chimera containing the extracellular and box1 domains of the Epo-R (Jak2-associated receptor) and the box2 and carboxyl-terminal domains of the interleukin 2 beta-receptor (IL2beta-R; a Jak1-associated subunit) is shown to activate Jak2. Interestingly, Jak2 also was activated in FDC-P1 cells by a control Epo-R chimera containing the complete IL2beta-R cytoplasmic domain, and mitogenesis was supported by each of these above chimeras. By comparison, in BaF3 cells expressing IL2 receptor alpha and gamma subunits, an ectopically expressed IL2beta-R chimera containing the box1 domain of the Epo-R, activated Jak2 and Jak3 and was as mitogenically active as the wild-type IL2beta-R (Jak1 and Jak3 activation). Thus, the box1 domain of the Epo-R specifies Jak2 activation and functions efficiently within a heterologous IL2 receptor complex that normally activates Jak1 and Jak3.
  • Authors

  • Jiang, N
  • He, TC
  • Miyajima, A
  • Wojchowski, Don
  • Status

    Publication Date

  • July 12, 1996
  • Published In


  • Amino Acid Sequence
  • Animals
  • Base Sequence
  • Cell Line
  • DNA, Complementary
  • Enzyme Activation
  • Humans
  • Janus Kinase 2
  • Mice
  • Mitogens
  • Molecular Sequence Data
  • Protein-Tyrosine Kinases
  • Proto-Oncogene Proteins
  • Receptors, Erythropoietin
  • Receptors, Interleukin-2
  • Recombinant Fusion Proteins
  • Sequence Homology, Amino Acid
  • Digital Object Identifier (doi)

    Pubmed Id

  • 8663338
  • Start Page

  • 16472
  • End Page

  • 16476
  • Volume

  • 271
  • Issue

  • 28