Phosphoproteomic analysis identifies Grb10 as an mTORC1 substrate that negatively regulates insulin signaling. Yu Y et al. 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.
General function
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Cellular localization
Cytoplasmic
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Ovarian function
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Expression regulated by
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Ovarian localization
Oocyte
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Shen WJ, et al reported expression of imprinted gene Grb10 in human oocytes and preimplantation embryos.
OBJECTIVE: To investigate the mRNA expression of imprinted gene Grb10, a candidate gene for Silver-Russell syndrome (SRS), in human oocytes and preimplantation embryos for understanding the role of Grb10 in embryogenesis and assisted reproductive technology (ART). METHODS: Nested reverse transcriptase (RT)-PCR was used to analyze Grb10 gene expression in human oocytes and preimplantation embryos. RESULTS: The transcripts of Grb10 were detected in human oocytes and preimplantation embryos at all stages except for the 2-cell stage. CONCLUSION: Grb10 gene is expressed in preimplantation embryos with close association with embryogenesis.