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Blood, 15 August 2000, Vol. 96, No. 4, pp. 1588-1590
BRIEF REPORT
Reassessment of interactions between hematopoietic
receptors using common beta-chain and interleukin-3-specific receptor
beta-chain-null cells: no evidence of functional interactions with
receptors for erythropoietin, granulocyte colony-stimulating factor, or
stem cell factor
Clare L. Scott,
Lorraine Robb,
Bette Papaevangeliou,
Rachel Mansfield,
Nicos A. Nicola, and
C. Glenn Begley
From The Walter and Eliza Hall Institute of Medical
Research, The Cooperative Research Centre for Cellular Growth Factors,
and the Rotary Bone Marrow Research Laboratories Factors, PO Royal
Melbourne Hospital, Victoria, Australia.
Mice lacking both the gene encoding the shared receptor for
granulocyte macrophage-colony-stimulating factor (GM-CSF),
interleukin-3 (IL-3), and IL-5 common -chain
(Bc) and the gene for the IL-3 specific
receptor (BIL3) were generated. This was achieved by targeting the Bc locus in embryonic stem cells
that were heterozygous for a null mutation of BIL3. Cells
from mice generated with the doubly targeted embryonic stem cells were
unresponsive to all 3 cytokines. Considerable previous data suggested a
role for common beta-chain ( c) in modulating
signaling of cytokines including erythropoietin (EPO), G-CSF, and stem
cell factor (SCF). However, bone marrow cells from mice lacking
c and IL3 showed
normal responsiveness to these cytokines. Thus, there was no evidence
for a biologically significant interaction between signaling via
c or IL3 and
signaling by EPO, G-CSF, or SCF. Previously documented biochemical
phenomena, including receptor transmodulation, receptor
transphosphorylation, and even direct physical interaction, involving
the c/ IL-3 receptor systems do not reflect genuine
interactions of physiological significance in primary hematopoietic
cells. This study provided results that challenge conclusions
previously established using a variety of biochemical assays.

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