{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,7,28]],"date-time":"2026-07-28T16:47:15Z","timestamp":1785257235342,"version":"3.55.0"},"reference-count":47,"publisher":"Springer Science and Business Media LLC","issue":"3","license":[{"start":{"date-parts":[[2011,1,18]],"date-time":"2011-01-18T00:00:00Z","timestamp":1295308800000},"content-version":"tdm","delay-in-days":0,"URL":"http:\/\/www.springer.com\/tdm"}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Behav Genet"],"published-print":{"date-parts":[[2011,5]]},"DOI":"10.1007\/s10519-010-9440-3","type":"journal-article","created":{"date-parts":[[2011,1,17]],"date-time":"2011-01-17T05:14:22Z","timestamp":1295241262000},"page":"349-356","source":"Crossref","is-referenced-by-count":11,"title":["Conservation of Structural and Functional Elements of TSC1 and TSC2: A Bioinformatic Comparison Across Animal Models"],"prefix":"10.1007","volume":"41","author":[{"given":"Jaco","family":"Serfontein","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"R. Ellen R.","family":"Nisbet","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Christopher J.","family":"Howe","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Petrus J.","family":"de Vries","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"297","published-online":{"date-parts":[[2011,1,18]]},"reference":[{"issue":"14","key":"9440_CR1","doi-asserted-by":"crossref","first-page":"1692","DOI":"10.4161\/cc.6.14.4478","volume":"6","author":"PJ Aspuria","year":"2007","unstructured":"Aspuria PJ, Sato T, Tamanoi F (2007) The TSC\/Rheb\/TOR signaling pathway in fission yeast and mammalian cells. Cell Cycle 6(14):1692\u20131695","journal-title":"Cell Cycle"},{"key":"9440_CR2","doi-asserted-by":"crossref","first-page":"51372","DOI":"10.1074\/jbc.M303956200","volume":"278","author":"A Astrinidis","year":"2003","unstructured":"Astrinidis A, Senapedis W, Coleman TR, Henske EP (2003) Cell cycle-regulated phosphorylation of hamartin, the product of the tuberous sclerosis complex 1 gene, by cyclin-dependent kinase1\/cyclin B. J Biol Chem 278:51372\u201351379","journal-title":"J Biol Chem"},{"key":"9440_CR3","doi-asserted-by":"crossref","first-page":"667","DOI":"10.1073\/pnas.0409143102","volume":"102","author":"BA Ballif","year":"2005","unstructured":"Ballif BA, Roux PP, Berber SA, MacKeigan GP, Blenis J, Gygi SP (2005) Quantitative phosphorylation profiling of the ERK\/p90 ribosomal S6 kinase-signalling cassette and its targets, the tuberous sclerosis tumor suppressors. Proc Natl Acad Sci USA 102:667\u2013672","journal-title":"Proc Natl Acad Sci USA"},{"key":"9440_CR4","doi-asserted-by":"crossref","first-page":"14579","DOI":"10.1073\/pnas.0802668105","volume":"105","author":"A Barquilla","year":"2008","unstructured":"Barquilla A, Crespo JL, Navarro M (2008) Rapamycin inhibits trypanosome cell growth by preventing TOR complex 2 formation. Proc Natl Acad Sci USA 105:14579\u201314584","journal-title":"Proc Natl Acad Sci USA"},{"key":"9440_CR5","doi-asserted-by":"crossref","first-page":"56","DOI":"10.1016\/j.bbr.2009.11.009","volume":"208","author":"RE Blaser","year":"2010","unstructured":"Blaser RE, Chadwick L, McGinnis GC (2010) Behavioral measures of anxiety in zebrafish (Danio rerio). Behav Brain Res 208:56\u201362","journal-title":"Behav Brain Res"},{"key":"9440_CR6","doi-asserted-by":"crossref","first-page":"2740","DOI":"10.1093\/nar\/26.11.2740","volume":"26","author":"E Bornberg-Bauer","year":"1998","unstructured":"Bornberg-Bauer E, Rivals E, Vingron M (1998) Computational approaches to identify leucine zippers. Nucleic Acids Res 26:2740\u20132746","journal-title":"Nucleic Acids Res"},{"key":"9440_CR7","doi-asserted-by":"crossref","first-page":"279","DOI":"10.1083\/jcb.200507119","volume":"173","author":"SL Cai","year":"2006","unstructured":"Cai SL, Tee AR, Short JD, Bergeron JM, Kim J, Shen J, Guo R, Johnson CL, Kiguchi K, Walker CL (2006) Activity of TSC2 is inhibited by Akt-mediated phosphorylation and membrane partitioning. J Cell Biol 173:279\u2013289","journal-title":"J Cell Biol"},{"key":"9440_CR8","doi-asserted-by":"crossref","first-page":"1908","DOI":"10.1093\/hmg\/ddq066","volume":"19","author":"J Cao","year":"2010","unstructured":"Cao J, Gong L, Guo DC, Mietzsch U, Kuang SQ, Kwartler CS, Safi H, Estrera A, Gambello MJ, Milewicz DM (2010) Thoracic aortic disease in tuberous sclerosis complex: molecular pathogenesis and potential therapies in Tsc2\u00b1\u00a0mice. Hum Mol Genet 19:1908\u20131920","journal-title":"Hum Mol Genet"},{"key":"9440_CR9","doi-asserted-by":"crossref","first-page":"1345","DOI":"10.1056\/NEJMra055323","volume":"355","author":"PB Crino","year":"2006","unstructured":"Crino PB, Nathanson KL, Henske EP (2006) The tuberous sclerosis complex. N Engl J Med 355:1345\u20131356","journal-title":"N Engl J Med"},{"key":"9440_CR10","doi-asserted-by":"crossref","first-page":"275","DOI":"10.1016\/j.nurt.2010.05.001","volume":"7","author":"PJ Vries de","year":"2010","unstructured":"de Vries PJ (2010) Targeted treatments for cognitive and neurodevelopmental disorders in tuberous sclerosis complex. Neurotherapeutics 7:275\u2013282","journal-title":"Neurotherapeutics"},{"key":"9440_CR11","doi-asserted-by":"crossref","first-page":"319","DOI":"10.1016\/j.molmed.2007.06.003","volume":"13","author":"PJ Vries de","year":"2007","unstructured":"de Vries PJ, Howe CJ (2007) The tuberous sclerosis complex proteins\u2014a GRIPP on cognition and neurodevelopment. Trends Mol Med 13:319\u2013326","journal-title":"Trends Mol Med"},{"key":"9440_CR12","doi-asserted-by":"crossref","first-page":"2443","DOI":"10.1093\/hmg\/9.16.2443","volume":"9","author":"A Dodd","year":"2000","unstructured":"Dodd A, Curtis PM, Williams LC, Love DR (2000) Zebrafish: bridging the gap between development and disease. Hum Mol Genet 9:2443\u20132449","journal-title":"Hum Mol Genet"},{"key":"9440_CR13","doi-asserted-by":"crossref","first-page":"2479","DOI":"10.1101\/gad.1240504","volume":"18","author":"JX Dong","year":"2004","unstructured":"Dong JX, Pan DJ (2004) Tsc2 is not a critical target of Akt during normal Drosophila development. Genes Dev 18:2479\u20132484","journal-title":"Genes Dev"},{"key":"9440_CR14","doi-asserted-by":"crossref","first-page":"R220","DOI":"10.1093\/hmg\/ddl197","volume":"15","author":"BD Gelb","year":"2006","unstructured":"Gelb BD, Tartaglia M (2006) Noonan syndrome and related disorders: dysregulated RAS-mitogen activated protein kinase transduction. Hum Mol Genet 15:R220\u2013R226","journal-title":"Hum Mol Genet"},{"key":"9440_CR15","doi-asserted-by":"crossref","first-page":"25","DOI":"10.1016\/j.mce.2008.02.009","volume":"293","author":"LI Gilbert","year":"2008","unstructured":"Gilbert LI (2008) Drosophila is an inclusive model for human diseases, growth and development. Mol Cell Endocrinol 293:25\u201331","journal-title":"Mol Cell Endocrinol"},{"key":"9440_CR16","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1002\/ana.21317","volume":"62","author":"SM Goorden","year":"2007","unstructured":"Goorden SM, van Woerden GM, van der Weerd L, Cheadle JP, Elgersma Y (2007) Cognitive deficits in Tsc1+\/\u2212\u00a0mice in the absence of cerebral lesions and seizures. Ann Neurol 62:648\u2013655","journal-title":"Ann Neurol"},{"key":"9440_CR17","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.molcel.2008.03.003","volume":"30","author":"DM Gwinn","year":"2008","unstructured":"Gwinn DM, Shackelford DB, Egan DF, Mihaylova MM, Mery A, Vasquez DS, Turk BE, Shaw RJ (2008) AMPK phosphorylation of raptor mediates a metabolic checkpoint. Mol Cell 30:214\u2013226","journal-title":"Mol Cell"},{"key":"9440_CR18","doi-asserted-by":"crossref","first-page":"2899","DOI":"10.1093\/hmg\/10.25.2899","volume":"10","author":"AK Hodges","year":"2001","unstructured":"Hodges AK, Li S, Maynard J, Parry L, Braverman R, Cheadle JP, DeClue JE, Sampson JR (2001) Pathological mutations in TSC1 and TSC2 disrupt the interaction between hamartin and tuberin. Hum Mol Genet 10:2899\u20132905","journal-title":"Hum Mol Genet"},{"key":"9440_CR19","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1042\/BJ20080281","volume":"412","author":"J Huang","year":"2008","unstructured":"Huang J, Manning BD (2008) The TSC1\u2013TSC2 complex: a molecular switchboard controlling cell growth. Biochem J 412:179\u2013190","journal-title":"Biochem J"},{"key":"9440_CR20","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1038\/ncb839","volume":"4","author":"K Inoki","year":"2002","unstructured":"Inoki K, Li Y, Zhu T, Wu J, Guan KL (2002) TSC2 is phosphorylated and inhibited by Akt and suppresses mTOR signalling. Nat Cell Biol 4:648\u2013657","journal-title":"Nat Cell Biol"},{"key":"9440_CR21","doi-asserted-by":"crossref","first-page":"19","DOI":"10.1038\/ng1494","volume":"37","author":"K Inoki","year":"2005","unstructured":"Inoki K, Corradetti MN, Guan K (2005) Dysregulation of the TSC\u2013mTOR pathway in human disease. Nat Genet 37:19\u201324","journal-title":"Nat Genet"},{"key":"9440_CR22","doi-asserted-by":"crossref","first-page":"529","DOI":"10.1016\/S0092-8674(00)80657-1","volume":"96","author":"N Ito","year":"1999","unstructured":"Ito N, Rubin GM (1999) Gigas, a Drosophila homolog of tuberous sclerosis gene product-2, regulates the cell cycle. Cell 96:529\u2013539","journal-title":"Cell"},{"key":"9440_CR23","doi-asserted-by":"crossref","first-page":"1122","DOI":"10.1038\/ncb1183","volume":"6","author":"E Jacinto","year":"2004","unstructured":"Jacinto E, Loewith R, Schmidt A, Lin S, R\u00fcegg MA, Hall A, Hall MN (2004) Mammalian TOR complex 2 controls the actin cytoskeleton and is rapamycin insensitive. Nat Cell Biol 6:1122\u20131128","journal-title":"Nat Cell Biol"},{"key":"9440_CR24","doi-asserted-by":"crossref","first-page":"8573","DOI":"10.1073\/pnas.0503224102","volume":"102","author":"CM Johannessen","year":"2005","unstructured":"Johannessen CM, Reczek EE, James MF, Brems H, Legius E, Cichowski K (2005) The NF1 tumor suppressor critically regulates TSC2 and mTOR. Proc Natl Acad Sci USA 102:8573\u20138578","journal-title":"Proc Natl Acad Sci USA"},{"key":"9440_CR25","doi-asserted-by":"crossref","first-page":"440","DOI":"10.1016\/j.cell.2007.05.058","volume":"130","author":"DF Lee","year":"2007","unstructured":"Lee DF, Kuo HP, Chen CT et al (2007) IKKbeta suppression of TSC1 links inflammation and tumor angiogenesis via the TOR pathway. Cell 130:440\u2013455","journal-title":"Cell"},{"key":"9440_CR26","doi-asserted-by":"crossref","first-page":"13663","DOI":"10.1074\/jbc.M300862200","volume":"278","author":"Y Li","year":"2003","unstructured":"Li Y, Inoki K, Vatratsis P, Guan KL (2003) The p38 and MK2 kinase cascade phosphorylates tuberin, the tuberous sclerosis 2 gene product, and enhances its interaction with 14\u20133\u20133. J Biol Chem 278:13663\u201313671","journal-title":"J Biol Chem"},{"key":"9440_CR27","doi-asserted-by":"crossref","first-page":"7965","DOI":"10.1128\/MCB.24.18.7965-7975.2004","volume":"24","author":"Y Li","year":"2004","unstructured":"Li Y, Inoki K, Guan KL (2004) Biochemical and functional characterizations of small GTPase Rheb and TSC2 GAP activity. Mol Cell Biol 24:7965\u20137975","journal-title":"Mol Cell Biol"},{"key":"9440_CR28","doi-asserted-by":"crossref","first-page":"353","DOI":"10.1038\/nrg2091","volume":"8","author":"GJ Lieschke","year":"2007","unstructured":"Lieschke GJ, Currie PD (2007) Animal models of human disease: zebrafish swim into view. Nat Rev Genet 8:353\u2013367","journal-title":"Nat Rev Genet"},{"key":"9440_CR29","doi-asserted-by":"crossref","first-page":"1162","DOI":"10.1126\/science.252.5009.1162","volume":"252","author":"A Lupas","year":"1991","unstructured":"Lupas A, Van Dyke M, Stock J (1991) Predicting coiled coils from protein sequences. Science 252:1162\u20131164","journal-title":"Science"},{"key":"9440_CR30","doi-asserted-by":"crossref","first-page":"179","DOI":"10.1016\/j.cell.2005.02.031","volume":"121","author":"L Ma","year":"2005","unstructured":"Ma L, Chen Z, Erdjument-Bromage H, Tempst P, Pandolfi PP (2005) Phosphorylation and functional inactivation of TSC2 by Erk: implications for tuberous sclerosis and cancer pathogenesis. Cell 121:179\u2013193","journal-title":"Cell"},{"key":"9440_CR31","doi-asserted-by":"crossref","first-page":"107","DOI":"10.1016\/S0002-9440(10)62958-6","volume":"167","author":"BC Mak","year":"2005","unstructured":"Mak BC, Kenerson HL, Aicher LD, Barnes EA, Yeung RS (2005) Aberrant beta-catenin signalling in tuberous sclerosis. Am J Pathol 167:107\u2013116","journal-title":"Am J Pathol"},{"key":"9440_CR32","doi-asserted-by":"crossref","first-page":"151","DOI":"10.1016\/S1097-2765(02)00568-3","volume":"10","author":"BD Manning","year":"2002","unstructured":"Manning BD, Tee AR, Logsdon MN, Blenis J, Cantley LC (2002) Identification of the tuberous sclerosis complex-2 tumour suppressor gene product tuber in as a target of the phosphoinositide 3-kinase\/Akt pathway. Mol Cell 10:151\u2013162","journal-title":"Mol Cell"},{"key":"9440_CR33","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1016\/j.tig.2007.08.007","volume":"23","author":"W Martin","year":"2007","unstructured":"Martin W, Roettger M, Lockhart PJ (2007) A reality check for alignments and trees. Trends Genet 23:478\u2013480","journal-title":"Trends Genet"},{"key":"9440_CR34","doi-asserted-by":"crossref","first-page":"18478","DOI":"10.1074\/jbc.C800055200","volume":"283","author":"U Narayanan","year":"2008","unstructured":"Narayanan U, Nalavadi V, Nakamoto M, Thomas G, Ceman S, Bassell GJ, Warren ST (2008) S6K1 phosphorylates and regulates fragile X mental retardation protein (FMRP) with the neuronal protein synthesis-dependent mammalian target of rapamycin (mTOR) signaling cascade. J Biol Chem 283:18478\u201318482","journal-title":"J Biol Chem"},{"key":"9440_CR35","doi-asserted-by":"crossref","first-page":"17115","DOI":"10.1073\/pnas.0805239105","volume":"105","author":"J Newbern","year":"2008","unstructured":"Newbern J, Zhong J, Wickramasinghe SR, Li X, Wu Y, Samuels I, Cherosky N, Karlo JC, O\u2019Loughlin B, Wikenheiser J, Gargesha M, Doughman YQ, Charron J, Ginty DD, Watanabe M, Saitta SC, Sinder WD, Landreth GE (2008) Mouse and human phenotypes indicate a critical conserved role for ERK2 signaling in neural crest development. Proc Natl Acad Sci USA 105:17115\u201317120","journal-title":"Proc Natl Acad Sci USA"},{"key":"9440_CR36","doi-asserted-by":"crossref","first-page":"205","DOI":"10.1006\/jmbi.2000.4042","volume":"302","author":"C Notredame","year":"2000","unstructured":"Notredame C, Higgins DG, Heringa J (2000) T-Coffee: a novel method for fast and accurate multiple sequence alignment. J Mol Biol 302:205\u2013217","journal-title":"J Mol Biol"},{"key":"9440_CR37","doi-asserted-by":"crossref","first-page":"2444","DOI":"10.1073\/pnas.85.8.2444","volume":"85","author":"WR Pearson","year":"1988","unstructured":"Pearson WR, Lipman DJ (1988) Improved tools for biological sequence comparison. Proc Natl Acad Sci USA 85:2444\u20132448","journal-title":"Proc Natl Acad Sci USA"},{"key":"9440_CR38","doi-asserted-by":"crossref","first-page":"658","DOI":"10.1038\/ncb840","volume":"4","author":"CJ Potter","year":"2002","unstructured":"Potter CJ, Pedraza LG, Xu T (2002) Akt regulates growth by directly phosphorylating Tsc2. Nat Cell Biol 4:658\u2013665","journal-title":"Nat Cell Biol"},{"key":"9440_CR39","doi-asserted-by":"crossref","first-page":"308","DOI":"10.1136\/adc.2004.062968","volume":"92","author":"KR Prescott","year":"2007","unstructured":"Prescott KR, Wilkie AOM (2007) Genetic aspects of birth defects: new understandings of old problems. Arch Dis Child Fetal Neonatal Ed 92:308\u2013314","journal-title":"Arch Dis Child Fetal Neonatal Ed"},{"key":"9440_CR40","doi-asserted-by":"crossref","first-page":"13489","DOI":"10.1073\/pnas.0405659101","volume":"101","author":"PP Roux","year":"2004","unstructured":"Roux PP, Ballif BA, Anjum R, Gygi SP, Blenis J (2004) Tumor-promoting phorbol esters and activated Ras inactivate the tuberous sclerosis tumor suppressor complex via p90 ribosomal S6 kinase. Proc Natl Acad Sci USA 101:13489\u201313494","journal-title":"Proc Natl Acad Sci USA"},{"key":"9440_CR41","doi-asserted-by":"crossref","first-page":"e6305","DOI":"10.1371\/journal.pone.0006305","volume":"4","author":"S Schleich","year":"2009","unstructured":"Schleich S, Telemann AA (2009) Akt phosphorylates both Tsc1 and Tsc2 in Drosophila, but neither phosphorylation is required for normal animal growth. PLoS One 4:e6305","journal-title":"PLoS One"},{"issue":"128","key":"9440_CR42","doi-asserted-by":"crossref","first-page":"ra49","DOI":"10.1126\/scisignal.2000803","volume":"3","author":"J Serfontein","year":"2010","unstructured":"Serfontein J, Nisbet RER, Howe CJ, de Vries PJ (2010) Evolution of the TSC1\/TSC2-TOR signaling pathway. Sci Signal 3(128):ra49","journal-title":"Sci Signal"},{"key":"9440_CR43","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1471-2229-7-26","volume":"7","author":"R Sormani","year":"2007","unstructured":"Sormani R, Yao L, Menand B, Ennar N, Lecampion C, Meyer C, Robaglia C (2007) Saccharomyces cerevisiae FKBP12 binds Arabidopsis thaliana TOR and its expression in plants leads to rapamycin susceptibility. BMC Plant Biol 7:26","journal-title":"BMC Plant Biol"},{"key":"9440_CR44","doi-asserted-by":"crossref","first-page":"4876","DOI":"10.1093\/nar\/25.24.4876","volume":"25","author":"JD Thompson","year":"1997","unstructured":"Thompson JD, Gibson TJ, Plewniak F, Jeanmougin F, Higgins DG (1997) The Clustal X Windows interface: flexible strategies for multiple sequence alignment aided by quality analysis tools. Nucleic Acids Res 25:4876\u20134884","journal-title":"Nucleic Acids Res"},{"key":"9440_CR45","doi-asserted-by":"crossref","first-page":"12706","DOI":"10.1074\/jbc.M313874200","volume":"278","author":"M Slegtenhorst Van","year":"2004","unstructured":"Van Slegtenhorst M, Carr E, Stoyanova R, Kruger WD, Henske EP (2004) Tsc1+ and tsc2+ regulate arginine uptake and metabolism in Schizosaccharomyces pombe. J Biol Chem 278:12706\u201312713","journal-title":"J Biol Chem"},{"key":"9440_CR46","doi-asserted-by":"crossref","first-page":"471","DOI":"10.1016\/j.cell.2006.01.016","volume":"124","author":"S Wullschleger","year":"2006","unstructured":"Wullschleger S, Loewith R, Hall MN (2006) TOR signalling in growth and metabolism. Cell 124:471\u2013484","journal-title":"Cell"},{"issue":"24","key":"9440_CR47","doi-asserted-by":"crossref","first-page":"11074","DOI":"10.1073\/pnas.1005620107","volume":"107","author":"DM Young","year":"2010","unstructured":"Young DM, Schenk AK, Yang SB, Jan YN, Jan LY (2010) Altered ultrasonic vocalizations in a tuberous sclerosis mouse model of autism. Proc Natl Acad Sci USA 107(24):11074\u201311079","journal-title":"Proc Natl Acad Sci USA"}],"container-title":["Behavior Genetics"],"original-title":[],"language":"en","link":[{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10519-010-9440-3.pdf","content-type":"application\/pdf","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/article\/10.1007\/s10519-010-9440-3\/fulltext.html","content-type":"text\/html","content-version":"vor","intended-application":"text-mining"},{"URL":"http:\/\/link.springer.com\/content\/pdf\/10.1007\/s10519-010-9440-3","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,29]],"date-time":"2019-05-29T19:41:32Z","timestamp":1559158892000},"score":1,"resource":{"primary":{"URL":"http:\/\/link.springer.com\/10.1007\/s10519-010-9440-3"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2011,1,18]]},"references-count":47,"journal-issue":{"issue":"3","published-print":{"date-parts":[[2011,5]]}},"alternative-id":["9440"],"URL":"https:\/\/doi.org\/10.1007\/s10519-010-9440-3","relation":{},"ISSN":["0001-8244","1573-3297"],"issn-type":[{"value":"0001-8244","type":"print"},{"value":"1573-3297","type":"electronic"}],"subject":[],"published":{"date-parts":[[2011,1,18]]}}}