{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,2]],"date-time":"2026-10-02T19:20:01Z","timestamp":1790968801372,"version":"4.1.0"},"reference-count":35,"publisher":"National Academy of Sciences","issue":"29","content-domain":{"domain":["www.pnas.org"],"crossmark-restriction":true},"short-container-title":["Proc. Natl. Acad. Sci. U.S.A."],"published-print":{"date-parts":[[2004,7,20]]},"abstract":"<jats:p>\n                    Mosquitoes generate an enormous burden on human health worldwide. Disease-transmitting species use a reproductive strategy, termed anautogeny, that requires a blood meal to initiate egg maturation. Whereas this strategy is important for driving disease transmission, the molecular mechanisms underlying this phenomenon are still poorly understood. The production of yolk protein precursors (YPPs), a central event in egg maturation, is called vitellogenesis. YPPs are synthesized in the fat body, the insect analogue of the vertebrate liver. Mosquito vitellogenesis is regulated by the steroid hormone 20 hydroxyecdysone (20E). However, 20E alone is not capable of activating vitellogenesis\n                    <jats:italic>in vivo<\/jats:italic>\n                    . Here, we report that amino acid signaling through the nutrient-sensitive target of rapamycin (TOR) pathway is essential for the activation of YPP gene expression. An increase in extracellular amino acid levels, similar to the increase observed after a blood meal, is critical for 20E stimulation of YPP gene expression. Treatment with the TOR kinase inhibitor rapamycin significantly inhibits YPP expression. We used RNA interference to knockdown the expression of two key proteins of the TOR signaling pathway, TOR, and tuberous sclerosis complex 2. Knockdown of TOR inhibited amino acid stimulation while knockdown of tuberous sclerosis complex 2, a negative regulator of TOR signaling, resulted in enhanced YPP expression. Thus, amino acid-based TOR signaling regulates the activation of egg development after a blood meal, an adaptation to the unique life style of mosquitoes.\n                  <\/jats:p>","DOI":"10.1073\/pnas.0403460101","type":"journal-article","created":{"date-parts":[[2004,6,30]],"date-time":"2004-06-30T21:49:47Z","timestamp":1088632187000},"page":"10626-10631","update-policy":"https:\/\/doi.org\/10.1073\/pnas.cm10313","source":"Crossref","is-referenced-by-count":238,"title":["Target of rapamycin-mediated amino acid signaling in mosquito anautogeny"],"prefix":"10.1073","volume":"101","author":[{"given":"Immo A.","family":"Hansen","sequence":"first","affiliation":[{"name":"Department of Entomology and Program in Biochemistry and Molecular Biology, University of California, Riverside, CA 92506"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Geoffrey M.","family":"Attardo","sequence":"additional","affiliation":[{"name":"Department of Entomology and Program in Biochemistry and Molecular Biology, University of California, Riverside, CA 92506"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jong-Hwa","family":"Park","sequence":"additional","affiliation":[{"name":"Department of Entomology and Program in Biochemistry and Molecular Biology, University of California, Riverside, CA 92506"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Quan","family":"Peng","sequence":"additional","affiliation":[{"name":"Department of Entomology and Program in Biochemistry and Molecular Biology, University of California, Riverside, CA 92506"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Alexander S.","family":"Raikhel","sequence":"additional","affiliation":[{"name":"Department of Entomology and Program in Biochemistry and Molecular Biology, University of California, Riverside, CA 92506"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"341","published-online":{"date-parts":[[2004,6,30]]},"reference":[{"key":"e_1_3_2_1_2","doi-asserted-by":"crossref","unstructured":"Clements A. 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