{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,10,10]],"date-time":"2026-10-10T00:21:01Z","timestamp":1791591661519,"version":"4.3.4"},"reference-count":28,"publisher":"Cold Spring Harbor Laboratory","issue":"13","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Genes Dev."],"published-print":{"date-parts":[[2004,7,1]]},"abstract":"<jats:p>\n                    Tuberous sclerosis complex (TSC) and Peutz-Jeghers syndrome (PJS) are dominantly inherited benign tumor syndromes that share striking histopathological similarities. Here we show that\n                    <jats:italic>LKB1<\/jats:italic>\n                    , the gene mutated in PJS, acts as a tumor suppressor by activating\n                    <jats:italic>TSC2<\/jats:italic>\n                    , the gene mutated in TSC. Like TSC2, LKB1 inhibits the phosphorylation of the key translational regulators S6K and 4EBP1. Furthermore, we show that LKB1 activates TSC2 through the AMP-dependent protein kinase (AMPK), indicating that LKB1 plays a role in cell growth regulation in response to cellular energy levels. Our results suggest that PJS and other benign tumor syndromes could be caused by dysregulation of the TSC2\/mTOR pathway.\n                  <\/jats:p>","DOI":"10.1101\/gad.1199104","type":"journal-article","created":{"date-parts":[[2004,7,1]],"date-time":"2004-07-01T17:39:37Z","timestamp":1088703577000},"page":"1533-1538","source":"Crossref","is-referenced-by-count":480,"title":["Regulation of the TSC pathway by LKB1: evidence of a molecular link between tuberous sclerosis complex and Peutz-Jeghers syndrome"],"prefix":"10.1101","volume":"18","author":[{"given":"Michael N.","family":"Corradetti","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ken","family":"Inoki","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Nabeel","family":"Bardeesy","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Ronald A.","family":"DePinho","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kun-Liang","family":"Guan","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"246","published-online":{"date-parts":[[2004,7,1]]},"reference":[{"key":"2021111607182421000_18.13.1533.1","doi-asserted-by":"publisher","DOI":"10.1038\/nature01045"},{"key":"2021111607182421000_18.13.1533.2","doi-asserted-by":"publisher","DOI":"10.1016\/S1535-6108(03)00187-9"},{"key":"2021111607182421000_18.13.1533.3","doi-asserted-by":"publisher","DOI":"10.1126\/science.1063518"},{"key":"2021111607182421000_18.13.1533.4","doi-asserted-by":"crossref","first-page":"182","DOI":"10.1016\/0016-5085(88)90628-2","volume":"94","year":"1988","journal-title":"Gastroenterology"},{"key":"2021111607182421000_18.13.1533.5","first-page":"5173","volume":"63","year":"2003","journal-title":"Cancer Res."},{"key":"2021111607182421000_18.13.1533.6","doi-asserted-by":"publisher","DOI":"10.1002\/humu.10257"},{"key":"2021111607182421000_18.13.1533.7","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M202678200"},{"key":"2021111607182421000_18.13.1533.8","doi-asserted-by":"publisher","DOI":"10.1002\/bies.10009"},{"key":"2021111607182421000_18.13.1533.9","doi-asserted-by":"publisher","DOI":"10.1186\/1475-4924-2-28"},{"key":"2021111607182421000_18.13.1533.10","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.1533136100"},{"key":"2021111607182421000_18.13.1533.11","doi-asserted-by":"publisher","DOI":"10.1016\/S1471-4892(03)00071-7"},{"key":"2021111607182421000_18.13.1533.12","doi-asserted-by":"publisher","DOI":"10.1038\/ncb839"},{"key":"2021111607182421000_18.13.1533.13","doi-asserted-by":"publisher","DOI":"10.1016\/S0092-8674(03)00929-2"},{"key":"2021111607182421000_18.13.1533.14","doi-asserted-by":"publisher","DOI":"10.1038\/nrm1018"},{"key":"2021111607182421000_18.13.1533.15","doi-asserted-by":"publisher","DOI":"10.1038\/ng0198-38"},{"key":"2021111607182421000_18.13.1533.16","first-page":"5645","volume":"62","year":"2002","journal-title":"Cancer Res."},{"key":"2021111607182421000_18.13.1533.17","doi-asserted-by":"publisher","DOI":"10.1046\/j.1469-1809.2003.00012.x"},{"key":"2021111607182421000_18.13.1533.18","doi-asserted-by":"publisher","DOI":"10.1093\/hmg\/11.5.525"},{"key":"2021111607182421000_18.13.1533.19","doi-asserted-by":"publisher","DOI":"10.1038\/sj.emboj.7600110"},{"key":"2021111607182421000_18.13.1533.20","doi-asserted-by":"publisher","DOI":"10.1016\/S1097-2765(02)00568-3"},{"key":"2021111607182421000_18.13.1533.21","doi-asserted-by":"publisher","DOI":"10.1038\/ncb840"},{"key":"2021111607182421000_18.13.1533.22","doi-asserted-by":"publisher","DOI":"10.1016\/j.molcel.2003.08.016"},{"key":"2021111607182421000_18.13.1533.23","doi-asserted-by":"publisher","DOI":"10.1073\/pnas.0308061100"},{"key":"2021111607182421000_18.13.1533.24","doi-asserted-by":"publisher","DOI":"10.1074\/jbc.M204152200"},{"key":"2021111607182421000_18.13.1533.25","doi-asserted-by":"publisher","DOI":"10.1016\/j.cub.2003.10.031"},{"key":"2021111607182421000_18.13.1533.26","doi-asserted-by":"publisher","DOI":"10.1126\/science.1062074"},{"key":"2021111607182421000_18.13.1533.27","doi-asserted-by":"publisher","DOI":"10.1016\/S1357-4310(98)01245-3"},{"key":"2021111607182421000_18.13.1533.28","doi-asserted-by":"publisher","DOI":"10.1172\/JCI200113505"}],"container-title":["Genes &amp; Development"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/syndication.highwire.org\/content\/doi\/10.1101\/gad.1199104","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2021,11,16]],"date-time":"2021-11-16T10:18:39Z","timestamp":1637057919000},"score":1,"resource":{"primary":{"URL":"http:\/\/genesdev.cshlp.org\/lookup\/doi\/10.1101\/gad.1199104"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2004,7,1]]},"references-count":28,"journal-issue":{"issue":"13","published-print":{"date-parts":[[2004,7,1]]}},"alternative-id":["10.1101\/gad.1199104"],"URL":"https:\/\/doi.org\/10.1101\/gad.1199104","relation":{"has-review":[{"id-type":"doi","id":"10.3410\/f.1019894.227490","asserted-by":"object"}]},"ISSN":["0890-9369","1549-5477"],"issn-type":[{"value":"0890-9369","type":"print"},{"value":"1549-5477","type":"electronic"}],"subject":[],"published":{"date-parts":[[2004,7,1]]}}}