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Type: Journal article
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
Author: Blake, T.
Jenkins, B.
D'Andrea, R.
Gonda, T.
Citation: Journal of Leukocyte Biology, 2002; 72(6):1246-1255
Publisher: Federation Amer Soc Exp Biol
Issue Date: 2002
ISSN: 0741-5400
Statement of
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
RMID: 0020091831
Appears in Collections:Molecular and Biomedical Science publications

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