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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 beta -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 (beta c) in modulating signaling of cytokines including erythropoietin (EPO), G-CSF, and stem cell factor (SCF). However, bone marrow cells from mice lacking beta c and beta IL3 showed normal responsiveness to these cytokines. Thus, there was no evidence for a biologically significant interaction between signaling via beta c or beta 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 beta c/beta 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.

© 2000 by The American Society of Hematology.
 

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