ArticleThe Journal of biological chemistry2011
Pharmacological and genetic evaluation of proposed roles of mitogen-activated protein kinase/extracellular signal-regulated kinase kinase (MEK), extracellular signal-regulated kinase (ERK), and p90(RSK) in the control of mTORC1 protein signaling by phorbol esters.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 30 papers.
What it found
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Who cites it
30 citing papers in PubMed, 44 citations in OpenAlex.
- The myokine irisin ameliorates the secretory dysfunction of pancreatic β cells in experimental and human type 2 diabetes.Science advances · 2026Article
- Ribosomal S6 kinase 2-forkhead box protein O4 signaling pathway plays an essential role in melanogenesis.Scientific reports · 2024Article
- Defective synaptic plasticity in a model of Coffin-Lowry syndrome is rescued by simultaneously targeting PKA and MAPK pathways.Learning & memory (Cold Spring Harbor, N.Y.) · 2022Article
- DEPDC5-dependent mTORC1 signaling mechanisms are critical for the anti-seizure effects of acute fasting.Cell reports · 2022Article
- Beyond controlling cell size: functional analyses of S6K in tumorigenesis.Cell death & disease · 2022Review
- Article
- SOX9 Transcriptionally Regulates mTOR-Induced Proliferation of Basal Cell Carcinomas.The Journal of investigative dermatology · 2018Article
- Therapeutic Targeting of mTOR in T-Cell Acute Lymphoblastic Leukemia: An Update.International journal of molecular sciences · 2018Review
- PLK1 regulates spindle association of phosphorylated eukaryotic translation initiation factor 4E-binding protein and spindle function in mouse oocytes.American journal of physiology. Cell physiology · 2017Article
- TSC2/Rheb signaling mediates ERK-dependent regulation of mTORC1 activity in C2C12 myoblasts.FEBS open bio · 2017Article
- Co-ordinated activation of classical and novel PKC isoforms is required for PMA-induced mTORC1 activation.PloS one · 2017Article
- RSK-mediated down-regulation of PDCD4 is required for proliferation, survival, and migration in a model of triple-negative breast cancer.Oncotarget · 2016Article
- Bone and skeletal muscle: Key players in mechanotransduction and potential overlapping mechanisms.Bone · 2015Review
- Jatropha curcas Protein Concentrate Stimulates Insulin Signaling, Lipogenesis, Protein Synthesis and the PKCα Pathway in Rat Liver.Plant foods for human nutrition (Dordrecht, Netherlands) · 2015Article
- Dynamics of elongation factor 2 kinase regulation in cortical neurons in response to synaptic activity.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- BDNF stimulation of protein synthesis in cortical neurons requires the MAP kinase-interacting kinase MNK1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Tumor promoter-induced cellular senescence: cell cycle arrest followed by geroconversion.Oncotarget · 2014Article
- Eukaryotic elongation factor 2 kinase activity is controlled by multiple inputs from oncogenic signaling.Molecular and cellular biology · 2014Article
- Activation of Rheb, but not of mTORC1, impairs spine synapse morphogenesis in tuberous sclerosis complex.Scientific reports · 2014Article
- Impairing the production of ribosomal RNA activates mammalian target of rapamycin complex 1 signalling and downstream translation factors.Nucleic acids research · 2014Article
Corrections and comments
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Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
The mammalian target of rapamycin complex 1 (mTORC1) links the control of mRNA translation, cell growth, and metabolism to diverse stimuli. Inappropriate activation of mTORC1 can lead to cancer. Phorbol esters are naturally occurring products that act as potent tumor promoters. They activate isoforms of protein kinase C (PKCs) and stimulate the oncogenic MEK/ERK signaling cascade. They also activate mTORC1 signaling. Previous work indicated that mTORC1 activation by the phorbol ester PMA (phorbol 12-myristate 13-acetate) depends upon PKCs and may involve MEK. However, the precise mechanism(s) through which they activate mTORC1 remains unclear. Recent studies have implicated both the ERKs and the ERK-activated 90-kDa ribosomal S6 kinases (p90(RSK)) in activating mTORC1 signaling via phosphorylation of TSC2 (a regulator of mTORC1) and/or the mTORC1 component raptor. However, the relative importance of each of these kinases and phosphorylation events for the activation of mTORC1 signaling is unknown. The recent availability of MEK (PD184352) and p90(RSK) (BI-D1870) inhibitors of improved specificity allowed us to address the roles of these protein kinases in controlling mTORC1 in a variety of human and rodent cell types. In parallel, we used specific shRNAs against p90(RSK1) and p90(RSK2) to further test their roles in regulating mTORC1 signaling. Our data indicate that p90(RSKs) are dispensable for the activation of mTORC1 signaling by phorbol esters in all cell types tested. Our data also reveal striking diversity in the requirements for MEK/ERK in the control of mTORC1 between different cell types, pointing to additional signaling connections between phorbol esters and mTORC1, which do not involve MEK/ERK. This study provides important information for the design of efficient strategies to combat the hyperactivation of mTORC1 signaling by oncogenic pathways.
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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 Socratic graph.