Blood, 15 November 2001, Vol. 98, No. 10, pp. 3165-3168
BRIEF REPORT
Perverted responses of the human granulocyte-macrophage
colony-stimulating factor receptor in mouse cell lines due to
cross-species 
-subunit association
Barbara McClure,
Frank Stomski,
Angel Lopez, and
Joanna Woodcock
From the Cytokine Receptor Laboratory, Hanson Centre
for Cancer Research, Institute of Medical and Veterinary Science,
Adelaide, South Australia.
Transfected murine cell lines are commonly used to study the
function of many human cytokine or receptor mutants. This study reports
the inappropriate activation of the human granulocyte-macrophage colony-stimulating factor (hGM-CSF) receptor by the human GM-CSF antagonist, E21R, when the human receptor is introduced into the murine
cell line BaF-B03. E21R-induced proliferation of the BaF-B03 cells is
dependent on transfection with both hGM-CSF receptor 
and
c subunits. Studies on the underlying mechanism
revealed constitutive association between human and mouse
c and GM-CSF receptor-, tyrosine phosphorylation of
mouse and human c, and association of phosphorylated
mouse c into an activated human GM-CSF receptor complex
in response to E21R and GM-CSF. This interspecies receptor cross-talk
of receptor signaling subunits may produce misleading results and
emphasizes the need to use cell lines devoid of the cognate endogenous
receptors for functional analysis of ligand and receptor mutants.
