gp130 is the common signal-transducing receptor chain of interleukin (IL)-6-type cytokines. Here we describe, for the first time, a single amino acid substitution (Trp666 → Ala) in the membrane-proximal interbox1/2 region that abrogates activation of STAT (signal transducer and activator of transcription) transcription factors and the proliferative response of pro-B-cell transfectants. Moreover, association of the Janus kinase JAK1 is prevented. No signalling of heterodimeric IL-5 receptor (IL-5R)/gp130 chimaeras occurs in COS-7 cells, even when only a single cytoplasmic chain of a gp130 dimer contains the Trp666Ala mutation, indicating that it acts dominantly.

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