Tyrosines 905 and 915 of gp130 are required for maximum induction of m2 muscarinic acetylcholine receptor and VIP gene transcription by cytokines in neuronal cells.

1. Leukemia inhibitory factor action is mediated by a heterodimeric receptor consisting of two subunits, gp130 and the low-affinity leukemia inhibitory factor receptor (LIFR). 2. We used chimeric receptors containing the intracellular domain of either the LIFR or gp130 to identify regions of the receptors required for induction of the m2 muscarinic acetylcholine receptor gene in IMR-32 and SN56 neuronal cells. 3. While chimeric receptors containing the intracellular domain of gp130 were able to induce transcription from both the m2 and the vasoactive intestinal peptide (VIP) gene promoters, chimeric receptors containing the intracellular domain of the LIFR were incapable of mediating induction of the m2 gene despite being able to induce VIP transcription. 4. Deletion and mutagenesis studies identified two tyrosines, Y905 and Y915, which were required for maximal induction of the m2 and VIP genes. 5. Because Y905 and Y915 are reported to be the only tyrosine residues in gp130 that bind Stat1, these results suggest that this transcription factor plays a key role in the induction of transcription of both the m2 and the VIP genes.