Premium
Functional cross‐talk between cytokine receptors revealed by activating mutations in the extracellular domain of the β‐subunit of the GM‐CSF receptor
Author(s) -
Blake Timothy J.,
Jenkins Brendan J.,
D’Andrea Richard J.,
Gonda Thomas J.
Publication year - 2002
Publication title -
journal of leukocyte biology
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.819
H-Index - 191
eISSN - 1938-3673
pISSN - 0741-5400
DOI - 10.1189/jlb.72.6.1246
Subject(s) - erythropoietin receptor , biology , receptor , tyrosine phosphorylation , microbiology and biotechnology , cytokine receptor , phosphorylation , extracellular , signal transduction , mutant , cytokine , protein subunit , tyrosine , tyrosine kinase , biochemistry , immunology , gene
Several reports have suggested an interaction between the erythropoietin receptor (EpoR) and the shared signaling subunit (hβ c ) 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 hβ c 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 hβ c 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 hβ c on intracellular tyrosine residues, EpoR displays constitutive tyrosine phosphorylation. These observations suggest that JAK2 activation mediates cross‐talk between EC mutants of hβ c and EpoR. The implications of these data are discussed as are our findings that activated hβ c mutants can functionally interact with certain other cytokine receptors.