Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling Academic Article uri icon

Overview

MeSH Major

  • GRB10 Adaptor Protein
  • Insulin
  • Proteins
  • Signal Transduction

abstract

  • The evolutionarily conserved serine-threonine kinase mammalian target of rapamycin (mTOR) plays a critical role in regulating many pathophysiological processes. Functional characterization of the mTOR signaling pathways, however, has been hampered by the paucity of known substrates. We used large-scale quantitative phosphoproteomics experiments to define the signaling networks downstream of mTORC1 and mTORC2. Characterization of one mTORC1 substrate, the growth factor receptor-bound protein 10 (Grb10), showed that mTORC1-mediated phosphorylation stabilized Grb10, leading to feedback inhibition of the phosphatidylinositol 3-kinase (PI3K) and extracellular signal-regulated, mitogen-activated protein kinase (ERK-MAPK) pathways. Grb10 expression is frequently down-regulated in various cancers, and loss of Grb10 and loss of the well-established tumor suppressor phosphatase PTEN appear to be mutually exclusive events, suggesting that Grb10 might be a tumor suppressor regulated by mTORC1.

publication date

  • June 10, 2011

Research

keywords

  • Academic Article

Identity

Language

  • eng

PubMed Central ID

  • PMC3195509

Digital Object Identifier (DOI)

  • 10.1126/science.1199484

PubMed ID

  • 21659605

Additional Document Info

start page

  • 1322

end page

  • 6

volume

  • 332

number

  • 6035