mTOR Ser1261 is an AMPK-­ dependent phosphosite in mouse and human skeletal muscle not required for mTORC2 activity

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dc.contributor.authorLi, Jingwen
dc.contributor.authorMadsen, Agnete B.
dc.contributor.authorKnudsen, Jonas R.
dc.contributor.authorHenríquez-Olguín, Carlos
dc.contributor.authorPersson, Kaspar W.
dc.contributor.authorLi, Zhencheng
dc.contributor.authorRaun, Steffen H.
dc.contributor.authorLi, Tianjiao
dc.contributor.authorKiens, Bente
dc.contributor.authorWojtaszewski, Jørgen F. P.
dc.contributor.authorRichter, Erik A.
dc.contributor.authorNogara, Leonardo
dc.contributor.authorBlaauw, Bert
dc.contributor.authorOgasawara, Riki
dc.contributor.authorJensen, Thomas E.
dc.coverage.spatialUSA
dc.date.accessioned2025-12-05T13:05:56Z
dc.date.available2025-12-05T13:05:56Z
dc.date.issued2025-01-31
dc.description.abstractThe kinases AMPK, and mTOR as part of either mTORC1 or mTORC2, are major orchestrators of cellular growth and metabolism. Phosphorylation of mTOR Ser1261 is reportedly stimulated by both insulin and AMPK activation and a regulator of both mTORC1 and mTORC2 activity. Intrigued by the possibilities that Ser1261 might be a convergence point between insulin and AMPK signaling in skeletal muscle, we investigated the regulation and function of this site using a combination of human exercise, transgenic mouse, and cell culture models. Ser1261 phosphorylation on mTOR did not respond to insulin in any of our tested models, but instead responded acutely to contractile activity in human and mouse muscle in an AMPK activity-dependent manner. Contraction-stimulated mTOR Ser1261 phosphorylation in mice was decreased by Raptor muscle knockout (mKO) and increased by Raptor muscle overexpression, yet was not affected by Rictor mKO, suggesting most of Ser1261 phosphorylation occurs within mTORC1 in skeletal muscle. In accordance, HEK293 cells mTOR Ser1261Ala mutation strongly impaired phosphorylation of mTORC1 substrates but not mTORC2 substrates. However, neither mTORC1 nor mTORC2-dependent
dc.identifier.citationFASEB Journal, Vol. 39, N° 2 (2025) p. 1-13
dc.identifier.doihttps://doi.org/10.1096/fj.202402064R
dc.identifier.issn0892-6638
dc.identifier.orcidhttps://orcid.org/0000-0002-9315-9365
dc.identifier.urihttps://hdl.handle.net/20.500.12254/7392
dc.language.isoen
dc.publisherJohn Wiley & Sons Inc.
dc.rightsAtribución-NoComercial-CompartirIgual 3.0 Chile (CC BY-NC-SA 3.0 CL)
dc.rights.urihttp://creativecommons.org/licenses/by-nc-sa/3.0/cl/
dc.subjectmTOR
dc.subjectAMPK
dc.subjectPhosphorylation
dc.titlemTOR Ser1261 is an AMPK-­ dependent phosphosite in mouse and human skeletal muscle not required for mTORC2 activity
dc.typeArticle
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