Shc associates with the IL-3 receptor β subunit, SHIP and Gab2 following IL-3 stimulation:: Contribution of Shc PTB and SH2 domains

被引：21

作者：

Bone, H

Welham, MJ ^{[1
]}

机构：

[1] Univ Bath, Dept Pharm & Pharmacol, Bath BA2 7AY, Avon, England

[2] Univ Bristol, Dept Pathol & Microbiol, Bristol, Avon, England

来源：

CELLULAR SIGNALLING | 2000年 / 12卷 / 03期

基金：

英国生物技术与生命科学研究理事会;

关键词：

Shc; interleukin-3; receptor; SH2; PTB; protein interactions;

D O I：

10.1016/S0898-6568(99)00088-1

中图分类号：

Q2 [细胞生物学];

学科分类号：

071009 ; 090102 ;

摘要：

p46(Shc) and p52(Shc) become heavily tyrosine phosphorylated in response to interleukin 3 (IL-3) treatment. We have investigated the potential of Shc to integrate IL-3 signalling pathways and demonstrate that Shc associates with the beta subunits of the human (beta c) and murine (Aic2A) IL-3 receptors, SHIP and Gab2 following IL-3 stimulation. The interaction between Shc and the IL-3 receptor beta chains was direct, mediated by both the SH2 and PTB domains. Interaction with SHIP was via the Shc PTB domain and the Shc SH2 domain mediated the interaction with Gab2. Phosphopeptide competition studies suggest that the SH2 domain interacts primarily with tyrosine 612 of beta c (610 of Aic2A), and the PTB domain with tyrosine 577 of beta c (575 of Aic2A). PTB binding to IL-3R beta chains was of highest affinity, and appeared to play the primary role in binding. These findings suggest that Shc may play an important role in coordinately integrating IL-3 signalling pathways. (C) 2000 Elsevier Science Inc. All rights reserved.

引用

页码：183 / 194

页数：12

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