Leukemia inhibitory factor receptor is structurally related to the IL-6 signal transducer, gp130.

Abstract

Leukemia inhibitory factor (LIF) is a cytokine with a broad range of activities that in many cases parallel those of interleukin‐6 (IL‐6) although LIF and IL‐6 appear to be structurally unrelated. A cDNA clone encoding the human LIF receptor was isolated by expression screening of a human placental cDNA library. The LIF receptor is related to the gp130 ‘signal‐transducing’ component of the IL‐6 receptor and to the G‐CSF receptor, with the transmembrane and cytoplasmic regions of the LIF receptor and gp130 being most closely related. This relationship suggests a common signal transduction pathway for the two receptors and may help to explain similar biological effects of the two ligands. Murine cDNAs encoding soluble LIF receptors were isolated by cross‐hybridization and share 70% amino acid sequence identity to the human sequence.

The recurrent translocation t(5;8)(p13;q12) in pleomorphic adenomas results in upregulation of PLAG1 gene expression under control of the LIFR promoter

“…Subsequent nucleotide sequence analysis of the PCR products revealed that ectopic sequences were fused to the acceptor splice site of exon 3 of PLAG1 (see Figure 3). BLAST analysis of the ectopic sequences showed that they were identical to sequences of the ®rst exon of the gene for the leukemia inhibitory factor receptor (LIFR) (Gearing et al, 1991). LIFR has previously been mapped to chromosome 5p12-13 .…”

“…As a result, a new translocation partner of PLAG1 was identi®ed, i.e. the gene for the leukemia inhibitory factor receptor (LIFR), which has previously been mapped to 5p12-p13 (Gearing et al, 1991. We demonstrate that the expression of the PLAG1 gene is upregulated in the two pleomorphic adenomas with 5;8-translocations.…”

“…LIFR is the second translocation partner known for PLAG1; the ®rst one being the CTNNB1 gene, which is the translocation partner gene in adenomas with t(3;8)(p21;q12). The LIFR gene encodes the receptor for the leukemia inhibitory factor (LIF) (Gearing et al, 1991), a multi-functional member of the interleukin-6 (IL-6) cytokine family, which is involved in differentiation, survival, and proliferation of a wide variety of fetal and adult cells (reviewed by Gearing, 1993). Structurally, LIFR is a member of the hemopoietin family of receptors (Bazan, 1990;Cosman et al, 1990).…”

Interleukin‐6: Structure‐function relationships

“…There is a similar conservation of the angle between the two FN 111 domains of the binding domain in the (Hibi et al, 1990). the LIFR (Gearing et al, 1991), the OSMRP (Mosley et al, 1996), and the membrane bound receptors for IL-6 (Yamasaki et al, 1988), IL-I 1 (Chtrel et al, 1995). andCNTF (Davis et al, 1991).…”

“…Heterodimerization of gp130 with the LIFR is induced by LIF and CT-1, which first bind to the LlFR (Gearing et al, 1991;Pennica et al, 1995), and by OSM, which first binds to gp130 (Gearing et al, 1992). OSM also induces heterodimerization of @I30 with the OSMRP, an OSM-specific signaling receptor, (Mosley et al, 1996).…”