CLONING OF A MURINE IL-11 RECEPTOR ALPHA-CHAIN - REQUIREMENT FOR GP130 FOR HIGH-AFFINITY BINDING AND SIGNAL-TRANSDUCTION

An adult mouse liver cDNA library was screened with oligonucleotides c orresponding 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 a nd predicted structure to the a-chain of the IL-6 receptor and mRNA wa s expressed in the 3T3-L1 pre-adipocytic cell line and in a range of p rimary tissues. Expression of NR1 in the factor-dependent haemopoietic cell line Ba/F3 resulted in the generation of low affinity receptors for IL-11 (K-d approximate to 10 nM). The capacity to bind IL-11 with high affinity (K-d = 300-800 pM) appeared to require coexpression of b oth NR1 and gp130, the common subunit of the IL-6, leukaemia inhibitor y factor (LIF), oncostatin M (OSM) and ciliary neurotrophic factor (CN TF) receptors. The expression of both NR1 and gp130 was also necessary for Ba/F3 cells to proliferate and M1 cells to undergo macrophage dif ferentiation in response to IL-11.