Open AccessDistinct signaling by insulin and IGF-1 receptors and their extra- and intracellular domains
Author(s) -
Hirofumi Nagao,
Weikang Cai,
Nicolai J. Wewer Albrechtsen,
Martin Steger,
Thiago M. Batista,
Pei Hui,
Jonathan M. Dreyfuss,
Matthias Mann,
C. Ronald Kahn
Publication year - 2021
Publication title -
proceedings of the national academy of sciences of the united states of america
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 5.011
H-Index - 771
eISSN - 1091-6490
pISSN - 0027-8424
DOI - 10.1073/pnas.2019474118
Subject(s) - insulin like growth factor 1 receptor , microbiology and biotechnology , insulin receptor , biology , signal transduction , mtorc1 , receptor , g protein coupled receptor , phosphorylation , protein kinase b , proto oncogene proteins c akt , insulin , growth factor , biochemistry , endocrinology , insulin resistance
Significance Insulin and IGF-1 receptors share many downstream signaling pathways but have unique biological effects. Here, using global phosphoproteomics, we demonstrate that there are important differences in phosphorylation-mediated signaling between IR and IGF1R in both the basal and ligand-stimulated states involving multiple pathways of cellular regulation. Thus, mTORC1 and PIP3/AKT signaling, which are important in metabolism, are preferentially regulated by IR, while Rho GTPases, mitosis, and cell cycle proteins, which are involved in control of cellular growth, are preferentially regulated by IGF1R. These differences can be mapped to effects of both the extracellular and intracellular domains of these receptors. Thus, despite their high homology, IR and IGF1R preferentially regulate distinct networks of phosphorylation, contributing to the unique effects of these hormones.