A single amino acid substitution (Trp666 → Ala) In the interbox1/2 region of the interleukin-6 signal transducer gp130 abrogates binding of JAK1, and dominantly impairs signal transduction

被引：20

作者：

Haan, C ^{[1
]}

Hermanns, HM ^{[1
]}

Heinrich, PC ^{[1
]}

Behrmann, I ^{[1
]}

机构：

[1] Rhein Westfal TH Aachen, Dept Biochem, D-52074 Aachen, Germany

来源：

BIOCHEMICAL JOURNAL | 2000年 / 349卷 / 01期

关键词：

cytokine receptor; interleukins; Jak/STAT pathway; Janus kinase;

D O I：

10.1042/0264-6021:3490261

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

071010 ; 081704 ;

摘要：

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 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 (IL5R)/gp130 chimaeras occurs in COS-7 cells, even when only a single cytoplasmic chain of a gp 130 dimer contains the Trp(666)Ala mutation, indicating that it acts dominantly.

引用

页码：261 / 266

页数：6

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