IRS-1 Functions as a Molecular Scaffold to Coordinate IGF-I/IGFBP-2 Signaling During Osteoblast Differentiation

Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research
Gang XiDavid R Clemmons

Abstract

Insulin like growth factor I (IGF-I) and insulin like growth factor binding protein-2 (IGFBP-2) function coordinately to stimulate AKT and osteoblast differentiation. IGFBP-2 binding to receptor protein tyrosine phosphatase β (RPTPβ) stimulates polymerization and inactivation of phosphatase activity. Because phosphatase and tensin homolog (PTEN) is the primary target of RPTPβ, this leads to enhanced PTEN tyrosine phosphorylation and inactivation. However RPTPβ inactivation also requires IGF-I receptor activation. The current studies were undertaken to determine the mechanism by which IGF-I mediates changes in RPTPβ function in osteoblasts. IGFBP-2/IGF-I stimulated vimentin binding to RPTPβ and this was required for RPTPβ polymerization. Vimentin serine phosphorylation mediated its binding to RPTPβ and PKCζ was identified as the kinase that phosphorylated vimentin. To determine the mechanism underlying IGF-I stimulation of PKCζ-mediated vimentin phosphorylation, we focused on insulin receptor substrate-1 (IRS-1). IGF-I stimulated IRS-1 phosphorylation and recruitment of PKCζ and vimentin to phospho-IRS-1. IRS-1 immunoprecipitates containing PKCζ and vimentin were used to confirm that activated PKCζ directly phosphorylated viment...Continue Reading

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Citations

Dec 20, 2017·Journal of Molecular Endocrinology·L A Bach
Apr 24, 2018·Endocrine Reviews·Gherardo MazziottiAndrea Giustina
Dec 4, 2019·Journal of Bone and Mineral Research : the Official Journal of the American Society for Bone and Mineral Research·Gang XiDavid R Clemmons
May 5, 2016·The Journal of Biological Chemistry·Irene S Tobias, Alexandra C Newton
Oct 18, 2020·Current Osteoporosis Reports·Sarah E Little-LetsingerMaya Styner
Jul 2, 2021·Computational and Structural Biotechnology Journal·Nabarun ChakrabortyMelissa A Kacena

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