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Two distinct functional high affinity receptors for mouse interleukin-3 (IL-3)
1Department of Molecular Biology, DNAX Research Institute of Molecular and Cellular Biology, Palo Alto, CA 94304.
The EMBO Journal
|May 1, 1992
Summary
Researchers identified two distinct high-affinity interleukin-3 receptors (IL-3R) in mice, explaining differences from human IL-3R. This discovery reveals novel molecular mechanisms for IL-3 signaling in mice.
Area of Science:
- Immunology
- Molecular Biology
- Cell Biology
Background:
- The human interleukin-3 receptor (IL-3R) comprises an IL-3 specific alpha subunit and a common beta subunit (beta c).
- Mouse IL-3R signaling differs from humans, possessing two related genes (AIC2A and AIC2B) homologous to the human beta c gene.
Purpose of the Study:
- To identify the cDNA encoding a protein that forms a high-affinity IL-3R when coexpressed with AIC2A in mouse cells.
- To characterize the function and binding properties of the newly identified mouse IL-3R components.
Main Methods:
- Coexpression of AIC2A with a candidate cDNA (SUT-1) in COS7 cells to assess high-affinity IL-3 binding.
- Characterization of IL-3 binding affinities and signal transduction in mouse T cell lines (CTLL-2) expressing identified receptors.
Main Results:
- A novel cDNA, SUT-1, was identified, encoding a 70 kDa protein with weak homology to human IL-3R alpha.
- SUT-1 formed high-affinity IL-3 receptors with both AIC2A and AIC2B.
- Both AIC2A/SUT-1 and AIC2B/SUT-1 receptors on mouse T cells bound IL-3 with high affinity and transmitted growth signals.
Conclusions:
- The mouse possesses two distinct functional high-affinity IL-3 receptors, AIC2A/SUT-1 and AIC2B/SUT-1.
- These findings provide a molecular basis for observed differences in IL-3R function between mice and humans.