{"@context":{"@vocab":"https://cir.nii.ac.jp/schema/1.0/","rdfs":"http://www.w3.org/2000/01/rdf-schema#","dc":"http://purl.org/dc/elements/1.1/","dcterms":"http://purl.org/dc/terms/","foaf":"http://xmlns.com/foaf/0.1/","prism":"http://prismstandard.org/namespaces/basic/2.0/","cinii":"http://ci.nii.ac.jp/ns/1.0/","datacite":"https://schema.datacite.org/meta/kernel-4/","ndl":"http://ndl.go.jp/dcndl/terms/","jpcoar":"https://github.com/JPCOAR/schema/blob/master/2.0/"},"@id":"https://cir.nii.ac.jp/crid/1361418521363857536.json","@type":"Article","productIdentifier":[{"identifier":{"@type":"DOI","@value":"10.1101/gad.1110003"}},{"identifier":{"@type":"URI","@value":"https://syndication.highwire.org/content/doi/10.1101/gad.1110003"}},{"identifier":{"@type":"NAID","@value":"30018918361"}}],"dc:title":[{"@value":"Rheb GTPase is a direct target of TSC2 GAP activity and regulates mTOR signaling"}],"description":[{"type":"abstract","notation":[{"@value":"<jats:p>Tuberous sclerosis complex (TSC) is a genetic disease caused by mutation in either<jats:italic>TSC1</jats:italic>or<jats:italic>TSC2</jats:italic>. The TSC1 and TSC2 gene products form a functional complex and inhibit phosphorylation of S6K and 4EBP1. These functions of TSC1/TSC2 are likely mediated by mTOR. Here we report that TSC2 is a GTPase-activating protein (GAP) toward Rheb, a Ras family GTPase. Rheb stimulates phosphorylation of S6K and 4EBP1. This function of Rheb is blocked by rapamycin and dominant-negative mTOR. Rheb stimulates the phosphorylation of mTOR and plays an essential role in regulation of S6K and 4EBP1 in response to nutrients and cellular energy status. Our data demonstrate that Rheb acts downstream of TSC1/TSC2 and upstream of mTOR to regulate cell growth.</jats:p>"}]}],"creator":[{"@id":"https://cir.nii.ac.jp/crid/1381418521363857536","@type":"Researcher","foaf:name":[{"@value":"Ken Inoki"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418521363857539","@type":"Researcher","foaf:name":[{"@value":"Yong Li"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418521363857537","@type":"Researcher","foaf:name":[{"@value":"Tian Xu"}]},{"@id":"https://cir.nii.ac.jp/crid/1381418521363857538","@type":"Researcher","foaf:name":[{"@value":"Kun-Liang Guan"}]}],"publication":{"publicationIdentifier":[{"@type":"PISSN","@value":"08909369"},{"@type":"EISSN","@value":"15495477"}],"prism:publicationName":[{"@value":"Genes & Development"}],"dc:publisher":[{"@value":"Cold Spring Harbor Laboratory"}],"prism:publicationDate":"2003-07-17","prism:volume":"17","prism:number":"15","prism:startingPage":"1829","prism:endingPage":"1834"},"reviewed":"false","url":[{"@id":"https://syndication.highwire.org/content/doi/10.1101/gad.1110003"}],"createdAt":"2003-07-22","modifiedAt":"2021-11-16","relatedProduct":[{"@id":"https://cir.nii.ac.jp/crid/1050001202634312704","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@language":"en","@value":"TSC2/Rheb signaling mediates ERK-dependent regulation of mTORC1 activity in C2C12 myoblasts"},{"@value":"TSC2/Rheb signaling mediates ERK‐dependent regulation of mTORC1 activity in C2C12 myoblasts"}]},{"@id":"https://cir.nii.ac.jp/crid/1050568772252081664","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Mdm20 Stimulates PolyQ Aggregation via Inhibiting Autophagy Through Akt-Ser473 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Autophagy"}]},{"@id":"https://cir.nii.ac.jp/crid/1360848662872019456","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Distinctive Responses to Nitrogen Starvation in the Dominant Active Mutants of the Fission Yeast Rheb GTPase"}]},{"@id":"https://cir.nii.ac.jp/crid/1360857593776797952","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Mapping of mTOR drug targets: Featured platforms for anti-cancer drug discovery"}]},{"@id":"https://cir.nii.ac.jp/crid/1360865816784803456","@type":"Article","resourceType":"学術雑誌論文(journal article)","relationType":["isReferencedBy"],"jpcoar:relatedTitle":[{"@value":"Fission Yeast TORC1 Promotes Cell Proliferation through Sfp1, a Transcription Factor Involved in Ribosome Biogenesis"}]},{"@id":"https://cir.nii.ac.jp/crid/1360869854341271552","@type":"Article","resourceType":"学術雑誌論文(journal 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