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Citation
Vinayagam, A., Kulkarni, M.M., Sopko, R., Sun, X., Hu, Y., Nand, A., Villalta, C., Moghimi, A., Yang, X., Mohr, S.E., Hong, P., Asara, J.M., Perrimon, N. (2016). An Integrative Analysis of the InR/PI3K/Akt Network Identifies the Dynamic Response to Insulin Signaling.  Cell Rep. 16(11): 3062--3074.
FlyBase ID
FBrf0233454
Publication Type
Research paper
Abstract
Insulin regulates an essential conserved signaling pathway affecting growth, proliferation, and metabolism. To expand our understanding of the insulin pathway, we combine biochemical, genetic, and computational approaches to build a comprehensive Drosophila InR/PI3K/Akt network. First, we map the dynamic protein-protein interaction network surrounding the insulin core pathway using bait-prey interactions connecting 566 proteins. Combining RNAi screening and phospho-specific antibodies, we find that 47% of interacting proteins affect pathway activity, and, using quantitative phosphoproteomics, we demonstrate that ∼10% of interacting proteins are regulated by insulin stimulation at the level of phosphorylation. Next, we integrate these orthogonal datasets to characterize the structure and dynamics of the insulin network at the level of protein complexes and validate our method by identifying regulatory roles for the Protein Phosphatase 2A (PP2A) and Reptin-Pontin chromatin-remodeling complexes as negative and positive regulators of ribosome biogenesis, respectively. Altogether, our study represents a comprehensive resource for the study of the evolutionary conserved insulin network.
Graphical Abstract
Obtained with permission from Cell Press.
PubMed ID
PubMed Central ID
PMC5033061 (PMC) (EuropePMC)
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    Language of Publication
    English
    Additional Languages of Abstract
    Parent Publication
    Publication Type
    Journal
    Abbreviation
    Cell Rep.
    Title
    Cell reports
    ISBN/ISSN
    2211-1247
    Data From Reference
    Gene Groups (1)
    Genes (29)
    Physical Interactions (1808)
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