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26 results

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Page 1
AMPK-dependent phosphorylation of the GATOR2 component WDR24 suppresses glucose-mediated mTORC1 activation.
Dai X, Jiang C, Jiang Q, Fang L, Yu H, Guo J, Yan P, Chi F, Zhang T, Inuzuka H, Asara JM, Wang P, Guo J, Wei W. Dai X, et al. Nat Metab. 2023 Feb;5(2):265-276. doi: 10.1038/s42255-022-00732-4. Epub 2023 Feb 2. Nat Metab. 2023. PMID: 36732624 Free PMC article.
Phosphomimetic Wdr24(S155D) knock-in mice exhibit early embryonic lethality and reduced mTORC1 activity. ...Our findings reveal that AMPK-mediated phosphorylation of WDR24 modulates glucose-induced mTORC1 activation, thereby providing a rationale for targeting AMPK- …
Phosphomimetic Wdr24(S155D) knock-in mice exhibit early embryonic lethality and reduced mTORC1 activity. ...Our findings reveal that …
Structure of the nutrient-sensing hub GATOR2.
Valenstein ML, Rogala KB, Lalgudi PV, Brignole EJ, Gu X, Saxton RA, Chantranupong L, Kolibius J, Quast JP, Sabatini DM. Valenstein ML, et al. Nature. 2022 Jul;607(7919):610-616. doi: 10.1038/s41586-022-04939-z. Epub 2022 Jul 13. Nature. 2022. PMID: 35831510 Free PMC article.
Amino acids signal to mTORC1 through the Rag GTPases, which are regulated by several protein complexes, including GATOR1 and GATOR2. GATOR2, which has five components (WDR24, MIOS, WDR59, SEH1L and SEC13), is required for amino acids to activate mTORC1 and interacts with t …
Amino acids signal to mTORC1 through the Rag GTPases, which are regulated by several protein complexes, including GATOR1 and GATOR2. GATOR2, …
Ring domains are essential for GATOR2-dependent mTORC1 activation.
Jiang C, Dai X, He S, Zhou H, Fang L, Guo J, Liu S, Zhang T, Pan W, Yu H, Fu T, Li D, Inuzuka H, Wang P, Xiao J, Wei W. Jiang C, et al. Mol Cell. 2023 Jan 5;83(1):74-89.e9. doi: 10.1016/j.molcel.2022.11.021. Epub 2022 Dec 16. Mol Cell. 2023. PMID: 36528027 Free PMC article.
Here, we report that disruption of the Ring domains of Mios, WDR24, or WDR59 completely impedes amino-acid-mediated mTORC1 activation. Mechanistically, via interacting with Ring domains of WDR59 and WDR24, the Ring domain of Mios acts as a hub to maintain GATOR2 int …
Here, we report that disruption of the Ring domains of Mios, WDR24, or WDR59 completely impedes amino-acid-mediated mTORC1 activation …
Sestrin2 is a leucine sensor for the mTORC1 pathway.
Wolfson RL, Chantranupong L, Saxton RA, Shen K, Scaria SM, Cantor JR, Sabatini DM. Wolfson RL, et al. Science. 2016 Jan 1;351(6268):43-8. doi: 10.1126/science.aab2674. Epub 2015 Oct 8. Science. 2016. PMID: 26449471 Free PMC article.
Mycobacterium tuberculosis produces D-serine under hypoxia to limit CD8+ T cell-dependent immunity in mice.
Cheng H, Ji Z, Wang Y, Li S, Tang T, Wang F, Peng C, Wu X, Cheng Y, Liu Z, Ma M, Wang J, Huang X, Wang L, Qin L, Liu H, Chen J, Zheng R, Feng CG, Cai X, Qu D, Ye L, Yang H, Ge B. Cheng H, et al. Nat Microbiol. 2024 Jul;9(7):1856-1872. doi: 10.1038/s41564-024-01701-1. Epub 2024 May 28. Nat Microbiol. 2024. PMID: 38806671 Free PMC article.
Mechanistically, D-serine interacted with WDR24 and inhibited mTORC1 activation in CD8(+) T cells. This decreased T-bet expression and reduced IFN-gamma production by CD8(+) T cells. ...
Mechanistically, D-serine interacted with WDR24 and inhibited mTORC1 activation in CD8(+) T cells. This decreased T-bet expression an …
CDK5-PRMT1-WDR24 signaling cascade promotes mTORC1 signaling and tumor growth.
Yin S, Liu L, Ball LE, Wang Y, Bedford MT, Duncan SA, Wang H, Gan W. Yin S, et al. Cell Rep. 2023 Apr 25;42(4):112316. doi: 10.1016/j.celrep.2023.112316. Epub 2023 Mar 29. Cell Rep. 2023. PMID: 36995937 Free PMC article.
In response to amino acids, cyclin-dependent kinase 5 (CDK5) phosphorylates PRMT1 at S307 to promote PRMT1 translocation from nucleus to cytoplasm and lysosome, which in turn methylates WDR24, an essential component of GATOR2, to activate the mTORC1 pathway. Disruption of …
In response to amino acids, cyclin-dependent kinase 5 (CDK5) phosphorylates PRMT1 at S307 to promote PRMT1 translocation from nucleus to cyt …
A Tumor suppressor complex with GAP activity for the Rag GTPases that signal amino acid sufficiency to mTORC1.
Bar-Peled L, Chantranupong L, Cherniack AD, Chen WW, Ottina KA, Grabiner BC, Spear ED, Carter SL, Meyerson M, Sabatini DM. Bar-Peled L, et al. Science. 2013 May 31;340(6136):1100-6. doi: 10.1126/science.1232044. Science. 2013. PMID: 23723238 Free PMC article.
In contrast, inhibition of GATOR2 subunits (Mios, WDR24, WDR59, Seh1L, and Sec13) suppresses mTORC1 signaling, and epistasis analysis shows that GATOR2 negatively regulates DEPDC5. ...
In contrast, inhibition of GATOR2 subunits (Mios, WDR24, WDR59, Seh1L, and Sec13) suppresses mTORC1 signaling, and epistasis analysis …
Genome-wide CRISPR screens identify ILF3 as a mediator of mTORC1-dependent amino acid sensing.
Yan G, Yang J, Li W, Guo A, Guan J, Liu Y. Yan G, et al. Nat Cell Biol. 2023 May;25(5):754-764. doi: 10.1038/s41556-023-01123-x. Epub 2023 Apr 10. Nat Cell Biol. 2023. PMID: 37037994
Adding a lysosome-targeting sequence to the GATOR2 component WDR24 bypasses the requirement for ILF3 to modulate amino-acid-dependent mTORC1 signalling. ...
Adding a lysosome-targeting sequence to the GATOR2 component WDR24 bypasses the requirement for ILF3 to modulate amino-acid-dependent …
Structural basis for the dynamic regulation of mTORC1 by amino acids.
Valenstein ML, Wranik M, Lalgudi PV, Linde-Garelli KY, Choi Y, Chivukula RR, Sabatini DM, Rogala KB. Valenstein ML, et al. Nature. 2025 Oct;646(8084):493-500. doi: 10.1038/s41586-025-09428-7. Epub 2025 Aug 20. Nature. 2025. PMID: 40836086 Free PMC article.
Binding of either sensor restricts the dynamic WDR24 beta-propeller of GATOR2, a domain essential for nutrient-dependent mTORC1 activation. ...
Binding of either sensor restricts the dynamic WDR24 beta-propeller of GATOR2, a domain essential for nutrient-dependent mTORC1 activ …
The GATOR2 Component Wdr24 Regulates TORC1 Activity and Lysosome Function.
Cai W, Wei Y, Jarnik M, Reich J, Lilly MA. Cai W, et al. PLoS Genet. 2016 May 11;12(5):e1006036. doi: 10.1371/journal.pgen.1006036. eCollection 2016 May. PLoS Genet. 2016. PMID: 27166823 Free PMC article.
Additionally, epistasis analysis between wdr24 and genes that encode components of the GATOR1 complex revealed that Wdr24 has a second critical function, the TORC1 independent regulation of lysosome dynamics and autophagic flux. ...Consistent with our findings in Dr …
Additionally, epistasis analysis between wdr24 and genes that encode components of the GATOR1 complex revealed that Wdr24 has …
26 results