biostudies-literatureUnknownTaylor MSNIDDK NIH HHSNIAID NIH HHSNCI NIH HHSNIGMS NIH HHSThe mTOR protein kinase forms two multiprotein complexes, mTORC1 and mTORC2, that function in distinct signaling pathways. mTORC1 is regulated by nutrients, and mTORC2 is a central node in phosphoinositide-3 kinase (PI3K) and small guanosine triphosphate Ras signaling networks commonly deregulated in cancer and diabetes. Although mTOR phosphorylates many substrates in vitro, in cells, mTORC1 and mTORC2 have high specificity: mTORC2 phosphorylates the protein kinases Akt and PKC, but not closely related kinases that are mTORC1 substrates. To understand how mTORC2 recognizes substrates, we created semisynthetic probes to trap the mTORC2-Akt complex and determine its structure. Whereas most protein kinases recognize amino acids adjacent to the phosphorylation site, local sequence contributes Science (New York, N.Y.)eadv7111https://www.ebi.ac.uk/biostudies/studies/S-EPMC12830033biostudies-literatureStructural basis for the recruitment and selective phosphorylation of Akt by mTORC2.PMC12830033R01 AI047389R00 CA255926R01 CA074305R01 CA129105R35 GM137905R35 GM150935T32 CA009302R01 CA103866R21 CA261737R01 CA233800K08 DK129824P30 CA124435R01 GM083960K22 CA241105F32 CA259214P41 GM109824Kondo KTLinde-Garelli KYMatas KCongreve Svan Eeuwen THancock MShi YXibinaku KSabatini DMTaylor MSFicarro SBChu NRogala KBFreund DO'Meara TRWranik MHennink MChen MSali ACole PAMarto JAPalanski BAGray NSMondal DMiller BDXiang YGroendyke BJValenstein MLLee MJfalseStructural basis for the recruitment and selective phosphorylation of Akt by mTORC2.The mTOR protein kinase forms two multiprotein complexes, mTORC1 and mTORC2, that function in distinct signaling pathways. mTORC1 is regulated by nutrients, and mTORC2 is a central node in phosphoinositide-3 kinase (PI3K) and small guanosine triphosphate Ras signaling networks commonly deregulated in cancer and diabetes. Although mTOR phosphorylates many substrates in vitro, in cells, mTORC1 and mTORC2 have high specificity: mTORC2 phosphorylates the protein kinases Akt and PKC, but not closely related kinases that are mTORC1 substrates. To understand how mTORC2 recognizes substrates, we created semisynthetic probes to trap the mTORC2-Akt complex and determine its structure. Whereas most protein kinases recognize amino acids adjacent to the phosphorylation site, local sequence contributes 2025-01-01T00:00:00Z2025 Nov2026-06-06T22:03:32.724Z2026-06-05T03:12:12.541ZS-EPMC128300334130812310.1126/science.adv7111