PEPTIDE INSERTIONS IN DOMAIN 4 OF hβc, THE SHARED SIGNALLING RECEPTOR SUBUNIT FOR GM-CSF, IL3 AND IL5, INDUCE LIGAND-INDEPENDENT ACTIVATION

Jones, Karen L.; Bagley, Christopher J.; Butcher, Carolyn M.; Barry, Simon C.; Vadas, Mathew A.; D’Andrea, Richard J.

doi:10.1006/cyto.2001.0913

Cited by 2 publications

(2 citation statements)

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“…We have previously shown that the EC mutants required association with the GMR␣ for their activity [17,18]. In addition, we showed that in contrast to WT h␤ c , the mutant forms of h␤ c could constitutively associate with murine GMR␣ (mGMR␣) [17].…”

Section: Discussionmentioning

confidence: 94%

“…At a cellular level, the erythrocytosis was a result of massively increased numbers and Epo independence of late erythroid progenitors [erythroid colony-forming units (CFU-E)]. However, our previous studies had indicated that this class of h␤ c mutant [extracellular (EC)] interacted with and required the GM-CSF receptor ␣ subunit (GMR␣) for activity [17,18]. As it is thought that CFU-E do not express GMR␣ [19], we wondered whether other CRs could also interact with the EC mutants and functionally substitute for GMR␣.…”

Section: Introductionmentioning

confidence: 99%

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Functional cross-talk between cytokine receptors revealed by activating mutations in the extracellular domain of the β-subunit of the GM-CSF receptor

Blake

Jenkins

D’Andrea

et al. 2002

Journal of Leukocyte Biology

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Several reports have suggested an interaction between the erythropoietin receptor (EpoR) and the shared signaling subunit (hβc) of the human granulocyte macrophage-colony stimulating factor (GM-CSF), interleukin (IL)-3, and IL-5 receptors, although the functional consequences of this interaction are unclear. We previously showed that in vivo expression of constitutively active extracellular (EC) mutants of hβc induces erythrocytosis and Epo independence of erythroid colony-forming units (CFU-E). This occurs despite an apparent requirement of these mutants for the GM-CSF receptor α-subunit (GMRα), which is not expressed in CFU-E. Here, we show that coexpression of hβc EC mutants and EpoR in BaF-B03 cells, which lack GMRα, results in factor-independent proliferation and JAK2 activation. Mutant receptors that cannot activate JAK2 fail to produce a functional interaction. As there is no detectable phosphorylation of hβc on intracellular tyrosine residues, EpoR displays constitutive tyrosine phosphorylation. These observations suggest that JAK2 activation mediates cross-talk between EC mutants of hβc and EpoR. The implications of these data are discussed as are our findings that activated hβc mutants can functionally interact with certain other cytokine receptors.

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Section: Discussionmentioning

confidence: 94%