Innate Immune Signaling in Drosophila Blocks Insulin Signaling by Uncoupling PI(3,4,5)P3 Production and Akt Activation

• DOI: 10.1016/j.celrep.2018.02.033
• Publication Date: 2018-03-06T20:38:16Z
• Authors: Stephen W. Roth; Moshe D. Bitterman; Morris J. Birnbaum; Michelle L. Bland
• Keywords: 0303 health sciences; QH301-705.5; Toll-Like Receptors; Mechanistic Target of Rapamycin Complex 2; Article; Immunity, Innate; Enzyme Activation; 03 medical and health sciences; Drosophila melanogaster; Phenotype; Phosphothreonine; Phosphatidylinositol Phosphates; Animals; Drosophila Proteins; Insulin; Biology (General); Phosphorylation; Proto-Oncogene Proteins c-akt; Signal Transduction

In obese adipose tissue, Toll-like receptor signaling in macrophages leads to insulin resistance adipocytes. Similarly, Toll the Drosophila larval fat body blocks insulin-dependent growth and nutrient storage. We find that acts cell autonomously block but not PI(3,4,5)P3 production cells expressing constitutively active PI3K. Fat whole-animal rictor mutants lacking TORC2 activity, larvae Pdk1. Phosphorylation of Akt on Pdk1 site, Thr342, is significantly reduced by signaling, expression mutant AktT342D rescues animal growth, storage, viability animals with signaling. Altogether, these data show innate immune at a more distal level than previously appreciated, they suggest manipulations affecting arm pathway may have profound effects sensitivity inflamed tissues.