ArticleMolecular and cellular biology2005
Distinct signaling events downstream of mTOR cooperate to mediate the effects of amino acids and insulin on initiation factor 4E-binding proteins.
Article in Molecular and cellular biology, 2005. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 85 papers.
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Who cites it
85 citing papers in PubMed, 206 citations in OpenAlex.
- Alcohol ingestion impairs maximal post-exercise rates of myofibrillar protein synthesis following a single bout of concurrent training.PloS one · 2014Trial
- Immobilization induces anabolic resistance in human myofibrillar protein synthesis with low and high dose amino acid infusion.The Journal of physiology · 2008Trial
- mTOR pathway candidate genes and energy intake interaction on breast cancer risk in Black women from the Women's Circle of Health Study.European journal of nutrition · 2023Article
- Delineating Structural Propensities of the 4E-BP2 Protein via Integrative Modeling and Clustering.The journal of physical chemistry. B · 2023Article
- mTOR pathway candidate genes and physical activity interaction on breast cancer risk in black women from the women's circle of health study.Breast cancer research and treatment · 2023Article
- CDK13 phosphorylates the translation machinery and promotes tumorigenic protein synthesis.Oncogene · 2023Article
- Targeting mTOR as a Cancer Therapy: Recent Advances in Natural Bioactive Compounds and Immunotherapy.Cancers · 2022Review
- mTOR pathway gene expression in association with race and clinicopathological characteristics in Black and White breast cancer patients.Discover oncology · 2022Article
- Mitosis-related phosphorylation of the eukaryotic translation suppressor 4E-BP1 and its interaction with eukaryotic translation initiation factor 4E (eIF4E).The Journal of biological chemistry · 2019Article
- Article
- Signaling Pathways Involved in the Regulation of mRNA Translation.Molecular and cellular biology · 2018Review
- Differential gene expression during early development in recently evolved and sympatric Arctic charr morphs.PeerJ · 2018Article
- Divergent Anabolic Signalling responses of Murine Soleus and Tibialis Anterior Muscles to Chronic 2G Hypergravity.Scientific reports · 2017Article
- Regulation of 4E-BP1 activity in the mammalian oocyte.Cell cycle (Georgetown, Tex.) · 2017Article
- mTORC1 signalling and eIF4E/4E-BP1 translation initiation factor stoichiometry influence recombinant protein productivity from GS-CHOK1 cells.The Biochemical journal · 2016Article
- Increased Skeletal Muscle GLUT4 Expression in Obese Mice After Voluntary Wheel Running Exercise Is Posttranscriptional.Diabetes · 2016Article
- Amino acid-dependent signaling via S6K1 and MYC is essential for regulation of rDNA transcription.Oncotarget · 2016Article
- GSK-3 directly regulates phospho-4EBP1 in renal cell carcinoma cell-line: an intrinsic subcellular mechanism for resistance to mTORC1 inhibition.BMC cancer · 2016Article
- Sirolimus and Everolimus Pathway: Reviewing Candidate Genes Influencing Their Intracellular Effects.International journal of molecular sciences · 2016Review
- In vivo AAV1 transduction with hRheb(S16H) protects hippocampal neurons by BDNF production.Molecular therapy : the journal of the American Society of Gene Therapy · 2015Article
25 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
5 authors at 2 institutions in 2 countries.
Funding
Abstract
Signaling through the mammalian target of rapamycin (mTOR) controls cell size and growth as well as other functions, and it is a potential therapeutic target for graft rejection, certain cancers, and disorders characterized by inappropriate cell or tissue growth. mTOR signaling is positively regulated by hormones or growth factors and amino acids. mTOR signaling regulates the phosphorylation of several proteins, the best characterized being ones that control mRNA translation. Eukaryotic initiation factor 4E-binding protein 1 (4E-BP1) undergoes phosphorylation at multiple sites. Here we show that amino acids regulate the N-terminal phosphorylation sites in 4E-BP1 through the RAIP motif in a rapamycin-insensitive manner. Several criteria indicate this reflects a rapamycin-insensitive output from mTOR. In contrast, the insulin-stimulated phosphorylation of the C-terminal site Ser64/65 is generally sensitive to rapamycin, as is phosphorylation of another well-characterized target for mTOR signaling, S6K1. Our data imply that it is unlikely that mTOR directly phosphorylates Thr69/70 in 4E-BP1. Although 4E-BP1 and S6K1 bind the mTOR partner, raptor, our data indicate that the outputs from mTOR to 4E-BP1 and S6K1 are distinct. In cells, efficient phosphorylation of 4E-BP1 requires it to be able to bind to eIF4E, whereas phosphorylation of 4E-BP1 by mTOR in vitro shows no such preference. These data have important implications for understanding signaling downstream of mTOR and the development of new strategies to impair mTOR signaling.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.