ArticleMolecular and cellular biology2009
Cell density-dependent inhibition of epidermal growth factor receptor signaling by p38alpha mitogen-activated protein kinase via Sprouty2 downregulation.
Article in Molecular and cellular biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
What it found
Each row is one number read from the abstract, on the scale the paper reported it, with its interval. Left of the dashed line favours the treatment, right favours the comparator. Under each row is the sentence it came from. New to these charts? A ten-minute tutorial.
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.
The trial behind it
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.
Neither the registry nor the abstract names a trial number. If this is a trial report, that itself is worth knowing.
Who cites it
31 citing papers in PubMed, 52 citations in OpenAlex.
- PKD phosphorylation and COP9/Signalosome modulate intracellular Spry2 protein stability.Oncogenesis · 2023Article
- Prolonged cetuximab treatment promotes p27Scientific reports · 2021Article
- MEK/ERK signaling is a critical regulator of high-risk human papillomavirus oncogene expression revealing therapeutic targets for HPV-induced tumors.PLoS pathogens · 2021Article
- The regulation of Net1/Cdc14 by the Hog1 MAPK upon osmostress unravels a new mechanism regulating mitosis.Cell cycle (Georgetown, Tex.) · 2020Review
- Distinct and sequential re-replication barriers ensure precise genome duplication.PLoS genetics · 2020Article
- The p38 Pathway: From Biology to Cancer Therapy.International journal of molecular sciences · 2020Review
- Agent-Based Models Predict Emergent Behavior of Heterogeneous Cell Populations in Dynamic Microenvironments.Frontiers in bioengineering and biotechnology · 2020Article
- Review
- The Effect of Calcium and Glucose Concentration on Corneal Epithelial Cell Lines Differentiation, Proliferation, and Focal Adhesion Expression.BioResearch open access · 2019Article
- G protein-coupled receptor kinase 4-induced cellular senescence and its senescence-associated gene expression profiling.Experimental cell research · 2017Article
- Cell type- and density-dependent effect of 1 T static magnetic field on cell proliferation.Oncotarget · 2017Article
- SIRT1 controls cell proliferation by regulating contact inhibition.Biochemical and biophysical research communications · 2016Article
- SPROUTY-2 represses the epithelial phenotype of colon carcinoma cells via upregulation of ZEB1 mediated by ETS1 and miR-200/miR-150.Oncogene · 2016Article
- Cell Density-Dependent Upregulation of PDCD4 in Keratinocytes and Its Implications for Epidermal Homeostasis and Repair.International journal of molecular sciences · 2015Article
- The comparison between dual inhibition of mTOR with MAPK and PI3K signaling pathways in KRAS mutant NSCLC cell lines.Tumour biology : the journal of the International Society for Oncodevelopmental Biology and Medicine · 2015Article
- Mechanisms of environmental chemicals that enable the cancer hallmark of evasion of growth suppression.Carcinogenesis · 2015Review
- Different Donor Cell Culture Methods Can Influence the Developmental Ability of Cloned Sheep Embryos.PloS one · 2015Article
- EGF potentiation of VEGF production is cell density dependent in H292 EGFR wild type NSCLC cell line.International journal of molecular sciences · 2014Article
- Toxicity of functional nano-micro zinc oxide tetrapods: impact of cell culture conditions, cellular age and material properties.PloS one · 2014Article
- Tuning of protein kinase circuitry by p38α is vital for epithelial tissue homeostasis.The Journal of biological chemistry · 2013Article
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Contact inhibition is a fundamental process in multicellular organisms aimed at inhibiting proliferation at high cellular densities through poorly characterized intracellular signals, despite availability of growth factors. We have previously identified the protein kinase p38alpha as a novel regulator of contact inhibition, as p38alpha is activated upon cell-cell contacts and p38alpha-deficient cells are impaired in both confluence-induced proliferation arrest and p27(Kip1) accumulation. Here, we establish that p27(Kip1) plays a key role downstream of p38alpha to arrest proliferation at high cellular densities. Surprisingly, p38alpha does not directly regulate p27(Kip1) expression levels but leads indirectly to confluent upregulation of p27(Kip1) and cell cycle arrest via the inhibition of mitogenic signals originating from the epidermal growth factor receptor (EGFR). Hence, confluent activation of p38alpha uncouples cell proliferation from mitogenic stimulation by inducing EGFR degradation through downregulation of the EGFR-stabilizing protein Sprouty2 (Spry2). Accordingly, confluent p38alpha-deficient cells fail to downregulate Spry2, providing them in turn with sustained EGFR signaling that facilitates cell overgrowth and oncogenic transformation. Our results provide novel mechanistic insight into the role of p38alpha as a sensor of cell density, which induces confluent cell cycle arrest via the Spry2-EGFR-p27(Kip1) network.
Indexed as
Identifiers
What OpenQuestion holds
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.