The box1 domain of the erythropoietin receptor specifies Janus kinase 2 activation and functions mitogenically within an interleukin 2 beta-receptor chimera.
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.
Jiang
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N
Graduate Program in Pathobiology, Pennsylvania State University, University Park, Pennsylvania 16802, USA.
He
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TC
Miyajima
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Wojchowski
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DM
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D002460:Cell Line; D018076:DNA, Complementary; D004789:Enzyme Activation; D006801:Humans; D053614:Janus Kinase 2; D051379:Mice; D008934:Mitogens / Q000502:physiology*; D008969:Molecular Sequence Data; D011505:Protein-Tyrosine Kinases / Q000378:metabolism*; D011518:Proto-Oncogene Proteins; D017467:Receptors, Erythropoietin / Q000235:genetics / Q000502:physiology*; D015375:Receptors, Interleukin-2 / Q000235:genetics*; D011993:Recombinant Fusion Proteins / Q000502:physiology*; D017386:Sequence Homology, Amino Acid
D018076:DNA, Complementary; D008934:Mitogens; D011518:Proto-Oncogene Proteins; D017467:Receptors, Erythropoietin; D015375:Receptors, Interleukin-2; D011993:Recombinant Fusion Proteins; D011505:Protein-Tyrosine Kinases; C507924:JAK2 protein, human; C507926:Jak2 protein, mouse; D053614:Janus Kinase 2