title: 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.
abstract: 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.
authors.affiliation: 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.
authors.forename: Fumihiko
authors.initials: F
authors.lastname: Hakuno
authors.affiliation: 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.
authors.forename: Toshiaki
authors.initials: T
authors.lastname: Fukushima
authors.affiliation: 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.
authors.forename: Yosuke
authors.initials: Y
authors.lastname: Yoneyama
authors.affiliation: 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.
authors.forename: Hiroyasu
authors.initials: H
authors.lastname: Kamei
authors.affiliation: 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.
authors.forename: Atsufumi
authors.initials: A
authors.lastname: Ozoe
authors.affiliation: Laboratory of Protein Metabolism, Tokyo Metropolitan Institute of Medical Science , Tokyo , Japan.
authors.forename: Hidehito
authors.initials: H
authors.lastname: Yoshihara
authors.affiliation: 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.
authors.forename: Daisuke
authors.initials: D
authors.lastname: Yamanaka
authors.affiliation: 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.
authors.forename: Takashi
authors.initials: T
authors.lastname: Shibano
authors.affiliation: 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.
authors.forename: Meri
authors.initials: M
authors.lastname: Sone-Yonezawa
authors.affiliation: 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.
authors.forename: Bu-Chin
authors.initials: BC
authors.lastname: Yu
authors.affiliation: 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.
authors.forename: Kazuhiro
authors.initials: K
authors.lastname: Chida
authors.affiliation: 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.
authors.forename: Shin-Ichiro
authors.initials: S
authors.lastname: Takahashi
keywords: IRS-associated protein; IRSome; cancer; insulin; insulin receptor substrate; insulin-like growth factor