Please use this identifier to cite or link to this item: https://hdl.handle.net/2440/82510
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dc.contributor.authorFonseca, B.-
dc.contributor.authorLee, V.-
dc.contributor.authorProud, C.-
dc.date.issued2008-
dc.identifier.citationBiochemical Journal, 2008; 411(1):141-149-
dc.identifier.issn0264-6021-
dc.identifier.issn1470-8728-
dc.identifier.urihttp://hdl.handle.net/2440/82510-
dc.description.abstractPRAS40 binds to the mTORC1 (mammalian target of rapamycin complex 1) and is released in response to insulin. It has been suggested that this effect is due to 14-3-3 binding and leads to activation of mTORC1 signalling. In a similar manner to insulin, phorbol esters also activate mTORC1 signalling, in this case via PKC (protein kinase C) and ERK (extracellular-signal-regulated kinase). However, phorbol esters do not induce phosphorylation of PRAS40 at Thr246, binding of 14-3-3 proteins to PRAS40 or its release from mTORC1. Mutation of Thr246 to a serine residue permits phorbol esters to induce phosphorylation and binding to 14-3-3 proteins. Such phosphorylation is apparently mediated by RSKs (ribosomal S6 kinases), which lie downstream of ERK. However, although the PRAS40(T246S) mutant binds to 14-3-3 better than wild-type PRAS40, each inhibits mTORC1 signalling to a similar extent. Our results show that activation of mTORC1 signalling by phorbol esters does not require PRAS40 to be phosphorylated at Thr246, bind to 14-3-3 or be released from mTORC1. It is conceivable that phorbol esters activate mTORC1by a distinct mechanism not involving PRAS40. Indeed, our results suggest that PRAS40 may not actually be involved in controlling mTORC1, but rather be a downstream target of mTORC1 that is regulated in response only to specific stimuli, such as insulin.-
dc.description.statementofresponsibilityBruno D. Fonseca, Vivian H.-Y. Lee and Christopher G. Proud-
dc.language.isoen-
dc.publisherPortland Press-
dc.rights© The Authors Journal compilation © 2008 Biochemical Society-
dc.source.urihttp://dx.doi.org/10.1042/bj20071001-
dc.subjectMammalian target of rapamycin (mTOR)-
dc.subjectmammalian target of rapamycin complex 1 (mTORC1)-
dc.subjectMAPK (mitogen-activated protein kinase)-
dc.subjectproline-rich Akt substrate of 40 kDa (PRAS40)-
dc.subjectphosphorylation, 14-3-3 protein-
dc.titleThe binding of PRAS40 to 14-3-3 proteins is not required for activation of mTORC1 signalling by phorbol esters/ERK-
dc.typeJournal article-
dc.identifier.doi10.1042/BJ20071001-
pubs.publication-statusPublished-
dc.identifier.orcidProud, C. [0000-0003-0704-6442]-
Appears in Collections:Aurora harvest
Molecular and Biomedical Science publications

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