ArticleGenes & development1998
4E-BP1, a repressor of mRNA translation, is phosphorylated and inactivated by the Akt(PKB) signaling pathway.
Article in Genes & development, 1998. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 374 papers, 2 of them syntheses that pooled it.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
374 citing papers in PubMed, 2 syntheses or guidelines pooled it, 885 citations in OpenAlex.
- Analysis from the perspective of cilia: the protective effect of PARP inhibitors on visual function during light-induced damage.International ophthalmology · 2020Pooled it
- Putative Mechanisms of Action and Clinical Use of Lithium in Children and Adolescents: A Critical Review.Current neuropharmacology · 2019Pooled it
- Article
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- Development of aBioactive materials · 2026Article
- eIF4A controls translation of estrogen receptor alpha and is a therapeutic target in advanced breast cancer.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
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- Dysregulated acetylcholine-mediated dopamine neurotransmission in the eIF4E Tg mouse model of autism spectrum disorders.Cell reports · 2024Article
- Liraglutide Protects Against Diastolic Dysfunction and Improves Ventricular Protein Translation.Cardiovascular drugs and therapy · 2024Article
- AKT kinases as therapeutic targets.Journal of experimental & clinical cancer research : CR · 2024Review
- The Spectrum of Renal "TFEopathies": Flipping the mTOR Switch in Renal Tumorigenesis.Physiology (Bethesda, Md.) · 2024Review
- PPM1G dephosphorylates eIF4E in control of mRNA translation and cell proliferation.Life science alliance · 2024Article
- Interplay between WNT/PI3K-mTOR axis and the microbiota in APC-driven colorectal carcinogenesis: data from a pilot study and possible implications for CRC prevention.Journal of translational medicine · 2024Article
- Retinoic acid signalling inhibits myogenesis by blocking MYOD translation in pig skeletal muscle cells.Animal biotechnology · 2024Article
- Multimodal stimulation screens reveal unique and shared genes limiting T cell fitness.Cancer cell · 2024Article
- Potential roles of UCH family deubiquitinases in tumorigenesis and chemical inhibitors developed against them.American journal of cancer research · 2024Review
- Spatiotemporal Regulation ofeNeuro · 2023Article
- Silibinin Downregulates Types I and III Collagen Expression via Suppression of the mTOR Signaling Pathway.International journal of molecular sciences · 2023Article
- WNK1 is required during male pachynema to sustain fertility.iScience · 2023Article
- Review
314 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
5 authors at 3 institutions in 2 countries.
Funding
Abstract
Growth factors and hormones activate protein translation by phosphorylation and inactivation of the translational repressors, the eIF4E-binding proteins (4E-BPs), through a wortmannin- and rapamycin-sensitive signaling pathway. The mechanism by which signals emanating from extracellular signals lead to phosphorylation of 4E-BPs is not well understood. Here we demonstrate that the activity of the serine/threonine kinase Akt/PKB is required in a signaling cascade that leads to phosphorylation and inactivation of 4E-BP1. PI 3-kinase elicits the phosphorylation of 4E-BP1 in a wortmannin- and rapamycin-sensitive manner, whereas activated Akt-mediated phosphorylation of 4E-BP1 is wortmannin resistant but rapamycin sensitive. A dominant negative mutant of Akt blocks insulin-mediated phosphorylation of 4E-BP1, indicating that Akt is required for the in vivo phosphorylation of 4E-BP1. Importantly, an activated Akt induces phosphorylation of 4E-BP1 on the same sites that are phosphorylated upon serum stimulation. Similar to what has been observed with serum and growth factors, phosphorylation of 4E-BP1 by Akt inhibits the interaction between 4E-BP1 and eIF-4E. Furthermore, phosphorylation of 4E-BP1 by Akt requires the activity of FRAP/mTOR. FRAP/mTOR may lie downstream of Akt in this signaling cascade. These results demonstrate that the PI 3-kinase-Akt signaling pathway, in concert with FRAP/mTOR, induces the phosphorylation of 4E-BP1.
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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.