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dc.contributor.authorNicklin, P.
dc.contributor.authorBergman, P.
dc.contributor.authorZhang, B.
dc.contributor.authorTriantafellow, E.
dc.contributor.authorWang, H.
dc.contributor.authorNyfeler, B.
dc.contributor.authorYang, H.
dc.contributor.authorHild, M.
dc.contributor.authorKung, C.
dc.contributor.authorWilson, C.
dc.contributor.authorMyer, V.E.
dc.contributor.authorMacKeigan, J.P.
dc.contributor.authorPorter, J.A.
dc.contributor.authorWang, Y.K.
dc.contributor.authorCantley, L.C.
dc.contributor.authorFinan, P.M.
dc.contributor.authorMurphy, L.O.
dc.identifier.citationNicklin , P , Bergman , P , Zhang , B , Triantafellow , E , Wang , H , Nyfeler , B , Yang , H , Hild , M , Kung , C , Wilson , C , Myer , V E , MacKeigan , J P , Porter , J A , Wang , Y K , Cantley , L C , Finan , P M & Murphy , L O 2009 , ' Bidirectional transport of amino acids regulates mTOR and autophagy ' , Cell , vol. 136 , no. 3 , pp. 521-534 .
dc.identifier.otherPURE: 2463748
dc.identifier.otherPURE UUID: a055b874-e355-420a-82dd-597c61e68763
dc.identifier.otherScopus: 59049087460
dc.description.abstractAmino acids are required for activation of the mammalian target of rapamycin (mTOR) kinase which regulates protein translation, cell growth, and autophagy. Cell surface transporters that allow amino acids to enter the cell and signal to mTOR are unknown. We show that cellular uptake of L-glutamine and its subsequent rapid efflux in the presence of essential amino acids (EAA) is the rate-limiting step that activates mTOR. L-glutamine uptake is regulated by SLC1A5 and loss of SLC1A5 function inhibits cell growth and activates autophagy. The molecular basis for L-glutamine sensitivity is due to SLC7A5/SLC3A2, a bidirectional transporter that regulates the simultaneous efflux of L-glutamine out of cells and transport of L-leucine/EAA into cells. Certain tumor cell lines with high basal cellular levels of L-glutamine bypass the need for L-glutamine uptake and are primed for mTOR activation. Thus, L-glutamine flux regulates mTOR, translation and autophagy to coordinate cell growth and proliferation.en
dc.titleBidirectional transport of amino acids regulates mTOR and autophagyen
dc.contributor.institutionSchool of Life and Medical Sciences
dc.contributor.institutionHealth & Human Sciences Research Institute
dc.contributor.institutionDepartment of Pharmacy
dc.description.statusPeer reviewed
dc.relation.schoolSchool of Life and Medical Sciences
rioxxterms.typeJournal Article/Review

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