PMID- 26074875 OWN - NLM STAT- PubMed-not-MEDLINE DCOM- 20150615 LR - 20181113 IS - 1664-2392 (Print) IS - 1664-2392 (Electronic) IS - 1664-2392 (Linking) VI - 6 DP - 2015 TI - The Novel Functions of High-Molecular-Mass Complexes Containing Insulin Receptor Substrates in Mediation and Modulation of Insulin-Like Activities: Emerging Concept of Diverse Functions by IRS-Associated Proteins. PG - 73 LID - 10.3389/fendo.2015.00073 [doi] LID - 73 AB - Insulin-like peptides, such as insulin-like growth factors (IGFs) and insulin, induce a variety of bioactivities, such as growth, differentiation, survival, increased anabolism, and decreased catabolism in many cell types and in vivo. In general, IGFs or insulin bind to IGF-I receptor (IGF-IR) or insulin receptor (IR), activating the receptor tyrosine kinase. Insulin receptor substrates (IRSs) are known to be major substrates of receptor kinases, mediating IGF/insulin signals to direct bioactivities. Recently, we discovered that IRSs form high-molecular-mass complexes (referred to here as IRSomes) even without IGF/insulin stimulation. These complexes contain proteins (referred to here as IRSAPs; IRS-associated proteins), which modulate tyrosine phosphorylation of IRSs by receptor kinases, control IRS stability, and determine intracellular localization of IRSs. In addition, in these complexes, we found not only proteins that are involved in RNA metabolism but also RNAs themselves. Thus, IRSAPs possibly contribute to modulation of IGF/insulin bioactivities. Since it is established that disorder of modulation of insulin-like activities causes various age-related diseases including cancer, we could propose that the IRSome is an important target for treatment of these diseases. FAU - Hakuno, Fumihiko AU - Hakuno F AD - Department of Animal Sciences, Graduate School of Agriculture and Life Sciences, The University of Tokyo , Tokyo , Japan ; Department of Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo , Tokyo , Japan. FAU - Fukushima, Toshiaki AU - Fukushima T AD - Laboratory of Biomedical Chemistry, Basic Life Sciences, Institute of Biomedical and Health Sciences, Hiroshima University , Hiroshima , Japan ; Department of Biological Sciences, Faculty of Bioscience and Biotechnology, Tokyo Institute of Technology , Kanagawa , Japan. FAU - Yoneyama, Yosuke AU - Yoneyama Y AD - Department of Animal Sciences, Graduate School of Agriculture and Life Sciences, The University of Tokyo , Tokyo , Japan ; Department of Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo , Tokyo , Japan. FAU - Kamei, Hiroyasu AU - Kamei H AD - Department of Animal Sciences, Graduate School of Agriculture and Life Sciences, The University of Tokyo , Tokyo , Japan ; Department of Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo , Tokyo , Japan. FAU - Ozoe, Atsufumi AU - Ozoe A AD - Department of Animal Sciences, Graduate School of Agriculture and Life Sciences, The University of Tokyo , Tokyo , Japan ; Department of Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo , Tokyo , Japan. FAU - Yoshihara, Hidehito AU - Yoshihara H AD - Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science , Tokyo , Japan. FAU - Yamanaka, Daisuke AU - Yamanaka D AD - Department of Animal Sciences, Graduate School of Agriculture and Life Sciences, The University of Tokyo , Tokyo , Japan ; Department of Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo , Tokyo , Japan. FAU - Shibano, Takashi AU - Shibano T AD - Department of Animal Sciences, Graduate School of Agriculture and Life Sciences, The University of Tokyo , Tokyo , Japan ; Department of Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo , Tokyo , Japan. FAU - Sone-Yonezawa, Meri AU - Sone-Yonezawa M AD - Department of Animal Sciences, Graduate School of Agriculture and Life Sciences, The University of Tokyo , Tokyo , Japan ; Department of Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo , Tokyo , Japan. FAU - Yu, Bu-Chin AU - Yu BC AD - Department of Animal Sciences, Graduate School of Agriculture and Life Sciences, The University of Tokyo , Tokyo , Japan ; Department of Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo , Tokyo , Japan. FAU - Chida, Kazuhiro AU - Chida K AD - Department of Animal Sciences, Graduate School of Agriculture and Life Sciences, The University of Tokyo , Tokyo , Japan ; Department of Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo , Tokyo , Japan. FAU - Takahashi, Shin-Ichiro AU - Takahashi S AD - Department of Animal Sciences, Graduate School of Agriculture and Life Sciences, The University of Tokyo , Tokyo , Japan ; Department of Applied Biological Chemistry, Graduate School of Agriculture and Life Sciences, The University of Tokyo , Tokyo , Japan. LA - eng PT - Journal Article PT - Review DEP - 20150526 PL - Switzerland TA - Front Endocrinol (Lausanne) JT - Frontiers in endocrinology JID - 101555782 PMC - PMC4443775 OTO - NOTNLM OT - IRS-associated protein OT - IRSome OT - cancer OT - insulin OT - insulin receptor substrate OT - insulin-like growth factor EDAT- 2015/06/16 06:00 MHDA- 2015/06/16 06:01 PMCR- 2015/01/01 CRDT- 2015/06/16 06:00 PHST- 2015/03/04 00:00 [received] PHST- 2015/04/25 00:00 [accepted] PHST- 2015/06/16 06:00 [entrez] PHST- 2015/06/16 06:00 [pubmed] PHST- 2015/06/16 06:01 [medline] PHST- 2015/01/01 00:00 [pmc-release] AID - 10.3389/fendo.2015.00073 [doi] PST - epublish SO - Front Endocrinol (Lausanne). 2015 May 26;6:73. doi: 10.3389/fendo.2015.00073. eCollection 2015.