Insulin receptor substrates form high-molecular-mass complexes that modulate their availability to insulin/insulin-like growth factor-I receptor tyrosine kinases

被引：27

作者：

Fukushima, Toshiaki ^{[2
,3
]}

Arai, Toshiya ^{[2
]}

Ariga-Nedachi, Miyako ^{[2
]}

Okajima, Hiroshi ^{[2
]}

Ooi, Yuko ^{[2
]}

Iijima, Yumi ^{[2
]}

Sone, Meri ^{[2
]}

Cho, Yoshitake ^{[2
]}

Ando, Yasutoshi ^{[2
]}

Kasahara, Kohei ^{[2
]}

Ozoe, Atsufumi ^{[2
]}

Yoshihara, Hidehito ^{[2
]}

Chida, Kazuhiro ^{[2
]}

Okada, Shigeru ^{[4
,5
]}

Kopchick, John J. ^{[4
,6
]}

Asano, Tomoichiro ^{[3
]}

Hakuno, Fumihiko ^{[2
]}

Takahashi, Shin-Ichiro ^{[1
,2
]}

机构：

[1] Univ Tokyo, Grad Sch Agr & Life Sci, Dept Anim Sci, Lab Cell Regulat,Bunkyo Ku, Tokyo 1138657, Japan

[2] Univ Tokyo, Grad Sch Agr & Life Sci, Dept Appl Biol Chem, Bunkyo Ku, Tokyo 1138657, Japan

[3] Hiroshima Univ, Grad Sch Med, Dept Med Sci, Hiroshima 7348553, Japan

[4] Ohio Univ, Edison Biotechnol Inst, Athens, OH 45701 USA

[5] Ohio Univ, Dept Pediat, Athens, OH 45701 USA

[6] Ohio Univ, Dept Biomed Sci, Athens, OH 45701 USA

来源：

BIOCHEMICAL AND BIOPHYSICAL RESEARCH COMMUNICATIONS | 2011年 / 404卷 / 03期

基金：

日本学术振兴会;

关键词：

Insulin receptor substrate (IRS); Insulin; Insulin-like growth factor (IGF); Tumor necrosis factor (TNF)-alpha; cAMP; Tyrosine phosphorylation; NECROSIS-FACTOR-ALPHA; SIGNALING PATHWAYS; ACTIVATION; PROTEINS; BINDING; PHOSPHORYLATION; ASSOCIATION; INHIBITION;

D O I：

10.1016/j.bbrc.2010.12.045

中图分类号：

Q5 [生物化学]; Q7 [分子生物学];

学科分类号：

070307 [化学生物学]; 071010 [生物化学与分子生物学];

摘要：

Insulin receptor substrates (IRSs) are phosphorylated by activated insulin/insulin-like growth factor (IGF)-I receptor tyrosine kinases. Phosphotyrosyl IRSs are recognized by signaling molecules possessing src homology region 2 (SH2) domains, which mediate various insulin/IGF bioactivities. However, we have shown that IRSs are also associated with other proteins by a phosphotyrosine-independent mechanism. Here, we demonstrated that IRSs form high-molecular-mass complexes (we named these complexes IRSomes) with various proteins and we elucidated their possible roles. Blue native-polyacrylamide gel electrophoresis of cell lysates revealed IRSome formation. Some proteins associated with IRSs in IRS-isoform-, cell-type-, or stimulus-specific manners. Results of the in vitro tyrosine phosphorylation assay indicated that tyrosine phosphorylation of IRS-1 by insulin receptor was decreased when IRS-1 was contained in IRSomes prepared from 3T3-L1 adipocytes treated with TNF-alpha. Also, tyrosine phosphorylation of IRS-2 by IGF-I receptor was increased when IRS-2 was contained in IRSomes prepared from FRTL-5 thyrocytes treated with dibutyryl cAMP. These results demonstrated that cytokine/hormone-induced formation of IRSomes modulates availability of IRSs to receptor tyrosine kinases. (C) 2010 Elsevier Inc. All rights reserved.

引用

页码：767 / 773

页数：7

共 21 条

[1]

Signalling pathways of insulin-like growth factor-I that are augmented by cAMP in FRTL-5 cells [J].