A single amino acid substitution (Trp(666) -> Ala) In the interbox1/2 region of the interleukin-6 signal transducer gp130 abrogates binding of JAK1, and dominantly impairs signal transduction

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 (Trp(666)-->Ala) in the membrane-proximal interbox1/2 region t hat abrogates activation of STAT (signal transducer and activator of transc ription) 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 (IL5R)/gp130 chimaeras occur s in COS-7 cells, even when only a single cytoplasmic chain of a gp 130 dim er contains the Trp(666)Ala mutation, indicating that it acts dominantly.