{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,1]],"date-time":"2026-07-01T21:42:22Z","timestamp":1782942142259,"version":"3.54.5"},"reference-count":59,"publisher":"American Society for Cell Biology (ASCB)","issue":"22","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["MBoC"],"published-print":{"date-parts":[[2018,11]]},"abstract":"<jats:p> TORC1 (target of rapamycin complex) integrates complex nutrient signals to generate and fine-tune a growth and metabolic response. Npr1 (nitrogen permease reactivator) is a downstream effector kinase of TORC1 that regulates the stability, activity, and trafficking of various nutrient permeases including the ammonium permeases Mep1, Mep2, and Mep3 and the general amino acid permease Gap1. Npr1 exerts its regulatory effects on Mep1 and Mep3 via Par32 (phosphorylated after rapamycin). Activation of Npr1 leads to phosphorylation of Par32, resulting in changes in its subcellular localization and function. Here we demonstrate that Par32 is a positive regulator of TORC1 activity. Loss of Par32 renders cells unable to recover from exposure to rapamycin and reverses the resistance to rapamycin of \u0394 npr1 cells. The sensitivity to rapamycin of cells lacking Par32 is dependent on Mep1 and Mep3 and the presence of ammonium, linking ammonium metabolism to TORC1 activity. Par32 function requires its conserved repeated glycine-rich motifs to be intact but, surprisingly, does not require its localization to the plasma membrane. In all, this work elucidates a novel mechanism by which Npr1 and Par32 exert regulatory feedback on TORC1. <\/jats:p>","DOI":"10.1091\/mbc.e18-03-0158","type":"journal-article","created":{"date-parts":[[2018,8,29]],"date-time":"2018-08-29T11:08:08Z","timestamp":1535540888000},"page":"2751-2765","source":"Crossref","is-referenced-by-count":15,"title":["Feedback regulation of TORC1 by its downstream effectors Npr1 and Par32"],"prefix":"10.1091","volume":"29","author":[{"given":"Natalia V.","family":"Varlakhanova","sequence":"first","affiliation":[{"name":"Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bryan A.","family":"Tornabene","sequence":"additional","affiliation":[{"name":"Department of Cell Biology, University of Pittsburgh School of Medicine, Pittsburgh, PA 15261"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Marijn G. 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