Structure of the mouse leukaemia inhibitory factor receptor gene:: regulated expression of mRNA encoding a soluble receptor isoform from an alternative 5′ untranslated region

The low-affinity leukaemia inhibitory factor receptor (LIF-R) is a component of cell-surface receptor complexes for the multifunctional cytokines leukaemia inhibitory factor, ciliary neurotrophic factor, oncostatin M and cardiotrophin-1. Both soluble and transmembrane forms of the protein have been described and several LIF-R mRNAs have been reported previously. In order to determine the coding potential of LIF-R mRNAs we have isolated and characterized the mouse LIF-R gene, mRNA encoding soluble LIF-R (sLIF-R) is formed by inclusion of an exon in which polyadenylation signals are provided by a B2 repeat, This exon is located centrally within the LIF-R gene but is excluded from the transmembrane LIF-R mRNA by alternative splicing, The transmembrane receptor is encoded by 19 exons distributed over 38 kb. Two distinct 5' non-coding exons have been identified, indicating the existence of alternative promoters. One of these is G/C rich and possesses a consensus initiator sequence as well as potential Spl binding sites. Expression of exon 1 from this promoter occurs in a wide variety of tissues, whereas expression of the alternative 5' untranslated region (exon la) is normally restricted to liver, the principal source of sLIF-R. During pregnancy expression of exon la becomes detectable also in the uterus. Expression of exon la increases dramatically during gestation and is accompanied by a similar quantitative rise in expression of sLIF-R mRNA. These findings establish that expression of LIF-R is under complex transcriptional control and indicate that regulated expression of the soluble cytokine receptor isoform may be due principally to an increase in the activity of a dedicated promoter.