Growth inhibition signalled through the interleukin-4/interleukin-13 receptor complex is associated with tyrosine phosphorylation of insulin receptor substrate-1

被引:20
作者
Schnyder, B
Lahm, H
Woerly, G
Odartchenko, N
Ryffel, B
Car, BD
机构
[1] SWISS FED INST TECHNOL,INST TOXICOL,CH-8603 SCHWERZENBACH,SWITZERLAND
[2] SWISS INST EXPTL CANC RES,LAUSANNE,SWITZERLAND
关键词
D O I
10.1042/bj3150767
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
Induction of growth inhibition in human colorectal carcinoma cell lines by interleukin (IL)-4 and IL-13 was associated with the neophosphorylation of a 170 kDa cellular protein, identified as insulin receptor substrate-1 (IRS-I) by immunoprecipitation. Tyrosine phosphorylation of IRS-I was also induced by insulin and insulin-like growth factor I. Sublines of colorectal carcinoma cells unresponsive to growth modulation by IL-4, IL-13 or insulin-like growth factor I-induced growth did not phosphorylate IRS-1. A functional, multimeric IL-4 receptor complex was present on all carcinoma cell lines with a subunit composition of 65 kDa, 75 kDa and the previously characterized 130 kDa band as demonstrated by affinity cross-linking with I-125-labelled IL-4. The 65 kDa subunit is novel whereas the 75 kDa band represents the common IL-2 receptor gamma-chain. The novel 65 kDa receptor was present as a double band and bound primarily I-125-labelled IL-13, The present study demonstrates the involvement of a novel chain other than the gamma-chain in the receptor complexes of IL-4 and IL-13 and post-receptor tyrosine phosphorylation of IRS-1. The association of IRS-1 with growth inhibitory signals in carcinoma cells suggests a novel mechanism of tumour growth control.
引用
收藏
页码:767 / 774
页数:8
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