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

Autor: Thomas J. Gonda, Brendan J. Jenkins, Timothy J. Blake, Richard J D'Andrea
Rok vydání: 2002
Předmět:
Zdroj: Journal of Leukocyte Biology. 72:1246-1255
ISSN: 1938-3673
0741-5400
Popis: 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.
Databáze: OpenAIRE
Externí odkaz: