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
- Author(s)
- Scott, CL; Robb, L; Papaevangeliou, B; Mansfield, R; Nicola, NA; Begley, CG;
- Details
- Publication Year 2000-08-15,Volume 96,Issue #4,Page 1588-1590
- Journal Title
- BLOOD
- Publication Type
- Journal Article
- Abstract
- Mice lacking both the gene encoding the shared receptor for granulocyte macrophage-colony-stimulating factor (GMCSF), interleukin-3 (IL-3), and IL-5 common beta-chain (B-c) and the gene for the IL-3 specific receptor (BIL3) were generated. This was achieved by targeting the B-c 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. (Blood. 2000;96:1588-1590) (C) 2000 by The American Society of Hematology.
- Publisher
- AMER SOC HEMATOLOGY
- Keywords
- GM-CSF RECEPTOR; TYROSINE PHOSPHORYLATION; DEFICIENT MICE; MAST-CELL; SUBUNIT; IL-3; PATHOLOGY; INVITRO; CLONING
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Creation Date: 2000-08-15 12:00:00