ArticleNature structural & molecular biology2013
Interaction with Shc prevents aberrant Erk activation in the absence of extracellular stimuli.
Article in Nature structural & molecular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 16 papers.
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Who cites it
16 citing papers in PubMed, 24 citations in OpenAlex.
- DDR1 sustains ferroptosis resistance in pancreatic ductal adenocarcinoma via SLC40A1-mediated iron homeostasis.Oncogene · 2026Article
- Receptor tyrosine kinases regulate signal transduction through a liquid-liquid phase separated state.Molecular cell · 2022Article
- Grb2 binding induces phosphorylation-independent activation of Shp2.Communications biology · 2021Article
- Mitogen-Inducible Gene 6 Inhibits Angiogenesis by Binding to SHC1 and Suppressing Its Phosphorylation.Frontiers in cell and developmental biology · 2021Article
- Mindin serves as a tumour suppressor gene during colon cancer progression through MAPK/ERK signalling pathway in mice.Journal of cellular and molecular medicine · 2020Article
- Targeting the Shc-EGFR interaction with indomethacin inhibits MAP kinase pathway signalling.Cancer letters · 2019Article
- Reductive Stress Selectively Disrupts Collagen Homeostasis and Modifies Growth Factor-independent Signaling Through the MAPK/Akt Pathway in Human Dermal Fibroblasts.Molecular & cellular proteomics : MCP · 2019Article
- GSK-3 promotes S-phase entry and progression inDevelopment (Cambridge, England) · 2018Article
- The role of the ShcD and RET interaction in neuroblastoma survival and migration.Biochemistry and biophysics reports · 2018Article
- Signaling adaptor ShcD suppresses extracellular signal-regulated kinase (Erk) phosphorylation distal to the Ret and Trk neurotrophic receptors.The Journal of biological chemistry · 2017Article
- Non-canonical dynamic mechanisms of interaction between the p66Shc protein and Met receptor.The Biochemical journal · 2016Article
- Effects of Resveratrol on p66Shc phosphorylation in cultured prostate cells.Translational medicine @ UniSa · 2015Article
- ShcA Protects against Epithelial-Mesenchymal Transition through Compartmentalized Inhibition of TGF-β-Induced Smad Activation.PLoS biology · 2015Article
- Grb2 monomer-dimer equilibrium determines normal versus oncogenic function.Nature communications · 2015Article
- Cytokine networking of chondrocyte dedifferentiation in vitro and its implications for cell-based cartilage therapy.American journal of translational research · 2015Review
- Cell signalling: SHC keeps ERK under control.Nature reviews. Molecular cell biology · 2013Article
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10 authors at 3 institutions in 2 countries.
Funding
Abstract
Control mechanisms that prevent aberrant signaling are necessary to maintain cellular homeostasis. We describe a new mechanism by which the adaptor protein Shc directly binds the MAP kinase Erk, thus preventing its activation in the absence of extracellular stimuli. The Shc-Erk complex restricts Erk nuclear translocation, restraining Erk-dependent transcription of genes, including those responsible for oncogenic growth. The complex forms through unique binding sites on both the Shc PTB domain and the N-terminal lobe of Erk. Upon receptor tyrosine kinase stimulation, a conformational change within Shc-induced through interaction with the phosphorylated receptor-releases Erk, allowing it to fulfill its role in signaling. Thus, in addition to its established role in promoting MAP kinase signaling in stimulated cells, Shc negatively regulates Erk activation in the absence of growth factors and thus could be considered a tumor suppressor in human cells.
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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.