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|Title:||Functional cross-talk between cytokine receptors revealed by activating mutations in the extracellular domain of the β-subunit of the GM-CSF receptor|
|Other Titles:||Functional cross-talk between cytokine receptors revealed by activating mutations in the extracellular domain of the beta-subunit of the GM-CSF receptor|
|Citation:||Journal of Leukocyte Biology, 2002; 72(6):1246-1255|
|Publisher:||Federation Amer Soc Exp Biol|
|Timothy J. Blake, Brendan J. Jenkins, Richard J. D’Andrea, and Thomas J. Gonda|
|Abstract:||Several reports have suggested an interaction between the erythropoietin receptor (EpoR) and the shared signaling subunit (hßc) 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 hßc 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 hßc 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 hßc on intracellular tyrosine residues, EpoR displays constitutive tyrosine phosphorylation. These observations suggest that JAK2 activation mediates cross-talk between EC mutants of hßc and EpoR. The implications of these data are discussed as are our findings that activated hßc mutants can functionally interact with certain other cytokine receptors.|
|Keywords:||erythropoietin receptor; factor independence; JAK2; tyrosine phosphorylation|
|Description:||© 2002 by Society for Leukocyte Biology|
|Appears in Collections:||Molecular and Biomedical Science publications|
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