{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,6]],"date-time":"2026-10-06T07:35:01Z","timestamp":1791272101964,"version":"4.1.0"},"reference-count":30,"publisher":"Springer Science and Business Media LLC","issue":"6","license":[{"start":{"date-parts":[[2003,5,27]],"date-time":"2003-05-27T00:00:00Z","timestamp":1053993600000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"},{"start":{"date-parts":[[2003,5,27]],"date-time":"2003-05-27T00:00:00Z","timestamp":1053993600000},"content-version":"vor","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":["link.springer.com"],"crossmark-restriction":false},"short-container-title":["Nat Cell Biol"],"published-print":{"date-parts":[[2003,6,1]]},"DOI":"10.1038\/ncb996","type":"journal-article","created":{"date-parts":[[2003,5,23]],"date-time":"2003-05-23T10:04:00Z","timestamp":1053684240000},"page":"566-571","update-policy":"https:\/\/doi.org\/10.1007\/springer_crossmark_policy","source":"Crossref","is-referenced-by-count":576,"title":["Rheb promotes cell growth as a component of the insulin\/TOR signalling network"],"prefix":"10.1038","volume":"5","author":[{"given":"Leslie J.","family":"Saucedo","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xinsheng","family":"Gao","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Dominic A.","family":"Chiarelli","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ling","family":"Li","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Duoija","family":"Pan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Bruce A.","family":"Edgar","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2003,5,27]]},"reference":[{"key":"BFncb996_CR1","doi-asserted-by":"crossref","first-page":"725","DOI":"10.1093\/genetics\/151.2.725","volume":"151","author":"G Toba","year":"1999","unstructured":"Toba, G. et al. The gene search system. A method for efficient detection and rapid molecular identification of genes in Drosophila melanogaster. Genetics 151, 725\u2013737 (1999).","journal-title":"Genetics"},{"key":"BFncb996_CR2","doi-asserted-by":"publisher","first-page":"651","DOI":"10.1016\/S0092-8674(00)81385-9","volume":"87","author":"M Freeman","year":"1996","unstructured":"Freeman, M. Reiterative use of the EGF receptor triggers differentiation of all cell types in the Drosophila eye. Cell 87, 651\u2013660 (1996).","journal-title":"Cell"},{"key":"BFncb996_CR3","doi-asserted-by":"crossref","first-page":"16333","DOI":"10.1016\/S0021-9258(17)34012-7","volume":"269","author":"K Yamagata","year":"1994","unstructured":"Yamagata, K. et al. rheb, a growth factor- and synaptic activity-regulated gene, encodes a novel Ras-related protein. J. Biol. Chem. 269, 16333\u201316339 (1994).","journal-title":"J. Biol. Chem."},{"key":"BFncb996_CR4","doi-asserted-by":"publisher","first-page":"221","DOI":"10.1016\/0014-5793(95)01349-0","volume":"377","author":"PS Gromov","year":"1995","unstructured":"Gromov, P.S., Madsen, P., Tomerup, N. & Celis, J.E. A novel approach for expression cloning of small GTPases: identification, tissue distribution and chromosome mapping of the human homolog of rheb. FEBS Lett. 377, 221\u2013226 (1995).","journal-title":"FEBS Lett."},{"key":"BFncb996_CR5","doi-asserted-by":"crossref","first-page":"271","DOI":"10.1242\/dev.124.2.271","volume":"124","author":"F Pignoni","year":"1997","unstructured":"Pignoni, F. & Zipursky, S.L. Induction of Drosophila eye development by decapentaplegic. Development 124, 271\u2013278 (1997).","journal-title":"Development"},{"key":"BFncb996_CR6","doi-asserted-by":"publisher","first-page":"1183","DOI":"10.1016\/S0092-8674(00)81462-2","volume":"93","author":"TP Neufeld","year":"1998","unstructured":"Neufeld, T.P., de la Cruz, A.F., Johnston, L.A. & Edgar, B.A. Coordination of growth and cell division in the Drosophila wing. Cell 93, 1183\u20131193 (1998).","journal-title":"Cell"},{"key":"BFncb996_CR7","doi-asserted-by":"publisher","first-page":"279","DOI":"10.1016\/S0959-437X(00)00191-X","volume":"11","author":"CJ Potter","year":"2001","unstructured":"Potter, C.J. & Xu, T. Mechanisms of size control. Curr. Opin. Genet. Dev. 11, 279\u2013286 (2001).","journal-title":"Curr. Opin. Genet. Dev."},{"key":"BFncb996_CR8","doi-asserted-by":"publisher","first-page":"239","DOI":"10.1016\/S1534-5807(02)00117-X","volume":"2","author":"JS Britton","year":"2002","unstructured":"Britton, J.S., Lockwood, W.K., Li, L., Cohen, S.M. & Edgar, B.A. Drosophila's Insulin\/PI3-Kinase pathway coordinates cellular metabolism with nutritional conditions. Dev. Cell 2, 239\u2013249 (2002).","journal-title":"Dev. Cell"},{"key":"BFncb996_CR9","doi-asserted-by":"publisher","first-page":"648","DOI":"10.1038\/ncb839","volume":"4","author":"K Inoki","year":"2002","unstructured":"Inoki, K., Li, Y., Zhu, T., Wu, J. & Guan, K.L. TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nature Cell Biol. 4, 648\u2013657 (2002).","journal-title":"Nature Cell Biol."},{"key":"BFncb996_CR10","doi-asserted-by":"publisher","first-page":"658","DOI":"10.1038\/ncb840","volume":"4","author":"CJ Potter","year":"2002","unstructured":"Potter, C.J., Pedraza, L.G. & Xu, T. Akt regulates growth by directly phosphorylating Tsc2. Nature Cell Biol. 4, 658\u2013665 (2002).","journal-title":"Nature Cell Biol."},{"key":"BFncb996_CR11","doi-asserted-by":"publisher","first-page":"151","DOI":"10.1016\/S1097-2765(02)00568-3","volume":"10","author":"BD Manning","year":"2002","unstructured":"Manning, B.D., Tee, A.R., Logsdon, M.N., Blenis, J. & Cantley, L.C. Identification of the tuberous sclerosis complex-2 tumor suppressor gene product tuberin as a target of the phosphoinositide 3-kinase\/akt pathway. Mol. Cell 10, 151\u2013162 (2002).","journal-title":"Mol. Cell"},{"key":"BFncb996_CR12","doi-asserted-by":"publisher","first-page":"357","DOI":"10.1016\/S0092-8674(01)00333-6","volume":"105","author":"CJ Potter","year":"2001","unstructured":"Potter, C.J., Huang, H. & Xu, T. Drosophila Tsc1 functions with Tsc2 to antagonize insulin signaling in regulating cell growth, cell proliferation, and organ size. Cell 105, 357\u2013368 (2001).","journal-title":"Cell"},{"key":"BFncb996_CR13","doi-asserted-by":"publisher","first-page":"1383","DOI":"10.1101\/gad.901101","volume":"15","author":"X Gao","year":"2001","unstructured":"Gao, X. & Pan, D. TSC1 and TSC2 tumor suppressors antagonize insulin signaling in cell growth. Genes Dev. 15, 1383\u20131392 (2001).","journal-title":"Genes Dev."},{"key":"BFncb996_CR14","doi-asserted-by":"publisher","first-page":"699","DOI":"10.1038\/ncb847","volume":"4","author":"X Gao","year":"2002","unstructured":"Gao, X. et al. Tsc tumour suppressor proteins antagonize amino-acid-TOR signalling. Nature Cell Biol. 4, 699\u2013704 (2002).","journal-title":"Nature Cell Biol."},{"key":"BFncb996_CR15","doi-asserted-by":"publisher","first-page":"2712","DOI":"10.1101\/gad.835000","volume":"14","author":"H Zhang","year":"2000","unstructured":"Zhang, H., Stallock, J.P., Ng, J.C., Reinhard, C. & Neufeld, T.P. Regulation of cellular growth by the Drosophila target of rapamycin dTOR. Genes Dev. 14, 2712\u20132724 (2000).","journal-title":"Genes Dev."},{"key":"BFncb996_CR16","doi-asserted-by":"publisher","first-page":"451","DOI":"10.1016\/S0896-6273(00)80701-1","volume":"22","author":"T Lee","year":"1999","unstructured":"Lee, T. & Luo, L. Mosaic analysis with a repressible cell marker for studies of gene function in neuronal morphogenesis. Neuron 22, 451\u2013461 (1999).","journal-title":"Neuron"},{"key":"BFncb996_CR17","doi-asserted-by":"publisher","first-page":"2689","DOI":"10.1101\/gad.845700","volume":"14","author":"S Oldham","year":"2000","unstructured":"Oldham, S., Montagne, J., Radimerski, T., Thomas, G. & Hafen, E. Genetic and biochemical characterization of dTOR, the Drosophila homolog of mammalian TOR. Genes Dev. 14, 2689\u20132694 (2000).","journal-title":"Genes Dev."},{"key":"BFncb996_CR18","doi-asserted-by":"publisher","first-page":"2126","DOI":"10.1126\/science.285.5436.2126","volume":"285","author":"J Montagne","year":"1999","unstructured":"Montagne, J. et al. Drosophila S6 kinase: a regulator of cell size. Science 285, 2126\u20132129 (1999).","journal-title":"Science"},{"key":"BFncb996_CR19","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1038\/ncb763","volume":"4","author":"T Radimerski","year":"2002","unstructured":"Radimerski, T. et al. dS6K-regulated cell growth is dPKB\/dPI(3)K-independent, but requires dPDK1. Nature Cell Biol. 4, 251\u2013255 (2002).","journal-title":"Nature Cell Biol."},{"key":"BFncb996_CR20","doi-asserted-by":"publisher","first-page":"207","DOI":"10.1016\/S1087-1845(02)00022-1","volume":"36","author":"JC Panepinto","year":"2002","unstructured":"Panepinto, J.C., Oliver, B.G., Amlung, T.W., Askew, D.S. & Rhodes, J.C. Expression of the Aspergillus fumigatus rheb homologue, rhbA, is induced by nitrogen starvation. Fungal Genet. Biol. 36, 207\u2013214 (2002).","journal-title":"Fungal Genet. Biol."},{"key":"BFncb996_CR21","doi-asserted-by":"publisher","first-page":"2286","DOI":"10.1101\/gad.991102","volume":"16","author":"DA Prober","year":"2002","unstructured":"Prober, D.A. & Edgar, B.A. Interactions between Ras1, dMyc, and PI3K in the developing Drosophila wing. Genes Dev. 16, 2286\u20132299 (2002).","journal-title":"Genes Dev."},{"key":"BFncb996_CR22","doi-asserted-by":"publisher","first-page":"600","DOI":"10.1038\/360600a0","volume":"360","author":"B Dickson","year":"1992","unstructured":"Dickson, B., Sprenger, F., Morrison, D. & Hafen, E. Raf functions downstream of Ras1 in the Sevenless signal transduction pathway. Nature 360, 600\u2013603 (1992).","journal-title":"Nature"},{"key":"BFncb996_CR23","doi-asserted-by":"publisher","first-page":"921","DOI":"10.1128\/MCB.17.2.921","volume":"17","author":"WM Yee","year":"1997","unstructured":"Yee, W.M. & Worley, P.F. Rheb interacts with Raf-1 kinase and may function to integrate growth factor- and protein kinase A-dependent signals. Mol. Cell Biol. 17, 921\u2013933 (1997).","journal-title":"Mol. Cell Biol."},{"key":"BFncb996_CR24","doi-asserted-by":"publisher","first-page":"10608","DOI":"10.1074\/jbc.272.16.10608","volume":"272","author":"GJ Clark","year":"1997","unstructured":"Clark, G.J. et al. The Ras-related protein Rheb is farnesylated and antagonizes Ras signaling and transformation. J. Biol. Chem. 272, 10608\u201310615 (1997).","journal-title":"J. Biol. Chem."},{"key":"BFncb996_CR25","doi-asserted-by":"publisher","first-page":"1991","DOI":"10.1093\/hmg\/6.11.1991","volume":"6","author":"MM Maheshwar","year":"1997","unstructured":"Maheshwar, M.M. et al. The GAP-related domain of tuberin, the product of the TSC2 gene, is a target for missense mutations in tuberous sclerosis. Hum. Mol. Genet. 6, 1991\u20131996 (1997).","journal-title":"Hum. Mol. Genet."},{"key":"BFncb996_CR26","doi-asserted-by":"publisher","first-page":"11198","DOI":"10.1074\/jbc.275.15.11198","volume":"275","author":"J Urano","year":"2000","unstructured":"Urano, J., Tabancay, A.P., Yang, W. & Tamanoi, F. The Saccharomyces cerevisiae Rheb G-protein is involved in regulating canavanine resistance and arginine uptake. J. Biol. Chem. 275, 11198\u201311206 (2000).","journal-title":"J. Biol. Chem."},{"key":"BFncb996_CR27","doi-asserted-by":"crossref","first-page":"611","DOI":"10.1093\/genetics\/155.2.611","volume":"155","author":"KE Mach","year":"2000","unstructured":"Mach, K.E., Furge, K.A. & Albright, C.F. Loss of Rhb1, a Rheb-related GTPase in fission yeast, causes growth arrest with a terminal phenotype similar to that caused by nitrogen starvation. Genetics 155, 611\u2013622 (2000).","journal-title":"Genetics"},{"key":"BFncb996_CR28","doi-asserted-by":"crossref","first-page":"461","DOI":"10.1093\/genetics\/118.3.461","volume":"118","author":"HM Robertson","year":"1988","unstructured":"Robertson, H.M. et al. A stable genomic source of P element transposase in Drosophila melanogaster. Genetics 118, 461\u2013470 (1988).","journal-title":"Genetics"},{"key":"BFncb996_CR29","doi-asserted-by":"publisher","first-page":"629","DOI":"10.1101\/gad.8.5.629","volume":"8","author":"AH Brand","year":"1994","unstructured":"Brand, A.H. & Perrimon, N. Raf acts downstream of the EGF receptor to determine dorsoventral polarity during Drosophila oogenesis. Genes Dev. 8, 629\u2013639 (1994).","journal-title":"Genes Dev."},{"key":"BFncb996_CR30","doi-asserted-by":"publisher","first-page":"404","DOI":"10.1006\/dbio.2000.9680","volume":"221","author":"X Gao","year":"2000","unstructured":"Gao, X., Neufeld, T.P. & Pan, D. Drosophila PTEN regulates cell growth and proliferation through PI3K- dependent and -independent pathways. Dev. Biol. 221, 404\u2013418 (2000).","journal-title":"Dev. Biol."}],"updated-by":[{"DOI":"10.1038\/ncb0703-680b","type":"erratum","label":"Erratum","source":"publisher","updated":{"date-parts":[[2003,7,1]],"date-time":"2003-07-01T00:00:00Z","timestamp":1057017600000}}],"container-title":["Nature Cell Biology"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/www.nature.com\/articles\/ncb996.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ncb996","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/www.nature.com\/articles\/ncb996.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2023,5,18]],"date-time":"2023-05-18T15:53:34Z","timestamp":1684425214000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.nature.com\/articles\/ncb996"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2003,5,27]]},"references-count":30,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2003,6,1]]}},"alternative-id":["BFncb996"],"URL":"https:\/\/doi.org\/10.1038\/ncb996","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1013733.191700","asserted-by":"object"},{"id-type":"doi","id":"10.3410\/f.1013733.793496367","asserted-by":"object"}]},"ISSN":["1465-7392","1476-4679"],"issn-type":[{"value":"1465-7392","type":"print"},{"value":"1476-4679","type":"electronic"}],"subject":[],"published":{"date-parts":[[2003,5,27]]},"assertion":[{"value":"27 January 2003","order":1,"name":"received","label":"Received","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"25 April 2003","order":2,"name":"accepted","label":"Accepted","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"27 May 2003","order":3,"name":"first_online","label":"First Online","group":{"name":"ArticleHistory","label":"Article History"}},{"value":"The authors declare no competing financial interests.","order":1,"name":"Ethics","group":{"name":"EthicsHeading","label":"Competing interests"}}]}}