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Cloning of a murine IL-11 receptor alpha-chain; requirement for gp130 for high affinity binding and signal
D J Hilton1, A A Hilton, A Raicevic
1Walter and Eliza Hall Institute of Medical Research, Parkville, Victoria.
Abstract:
An adult mouse liver cDNA library was screened with oligonucleotides corresponding to the conserved WSXWS motif of the haemopoietin receptor family. Using this method, cDNA clones encoding a novel receptor were isolated. The new receptor, named NR1, was most similar in sequence and predicted structure to the alpha-chain of the IL-6 receptor and mRNA was expressed in the 3T3-L1 pre-adipocytic cell line and in a range of primary tissues. Expression of NR1 in the factor-dependent haemopoietic cell line Ba/F3 resulted in the generation of low affinity receptors for IL-11 (Kd approximately 10 nM). The capacity to bind IL-11 with high affinity (Kd = 300-800 pM) appeared to require coexpression of both NR1 and gp130, the common subunit of the IL-6, leukaemia inhibitory factor (LIF), oncostatin M (OSM) and ciliary neurotrophic factor (CNTF) receptors. The expression of both NR1 and gp130 was also necessary for Ba/F3 cells to proliferate and M1 cells to undergo macrophage differentiation in response to IL-11.
Insights
Researchers identified a novel receptor, NR1, crucial for high-affinity interleukin-11 (IL-11) binding. Co-expression with gp130 is essential for IL-11 signaling, impacting cell proliferation and differentiation.
Area of Science:
- Molecular Biology
- Cell Biology
- Immunology
Background:
- Haemopoietin receptors mediate cellular responses to cytokines.
- The IL-6 receptor alpha-chain shares structural similarities with novel receptor families.
Purpose of the Study:
- To identify and characterize novel receptors within the haemopoietin receptor family.
- To elucidate the role of the novel receptor NR1 in IL-11 signaling.
Main Methods:
- Screening of a mouse liver cDNA library using WSXWS motif-specific oligonucleotides.
- Expression analysis of NR1 in various cell lines and primary tissues.
- Functional assays involving Ba/F3 and M1 cell lines to assess IL-11 receptor binding and signaling.
Main Results:
- A novel receptor, NR1, was isolated and found to be similar to the IL-6 receptor alpha-chain.
- NR1 expression alone conferred low-affinity IL-11 binding.
- High-affinity IL-11 binding and downstream signaling (proliferation, differentiation) required co-expression of NR1 and gp130.
Conclusions:
- NR1 is a component of the IL-11 receptor complex.
- The co-receptor gp130 is essential for high-affinity IL-11 binding and mediating IL-11-induced cellular responses.
