ArticleMolecular and cellular biology2001
Downregulation of the Ras-mitogen-activated protein kinase pathway by the EphB2 receptor tyrosine kinase is required for ephrin-induced neurite retraction.
Article in Molecular and cellular biology, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 73 papers.
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Who cites it
73 citing papers in PubMed, 188 citations in OpenAlex.
- A ternary association of KRas, EphA2, and integrins controls PDAC cell behavior.The Journal of biological chemistry · 2026Article
- FGF-Mediated Axon Guidance: Role of Downstream Signaling Pathways in Cytoskeletal Control.Cells · 2025Review
- Concerted transcriptional regulation of the morphogenesis of hypothalamic neurons by ONECUT3.Nature communications · 2024Article
- Article
- Recurring EPHB1 mutations in human cancers alter receptor signalling and compartmentalisation of colorectal cancer cells.Cell communication and signaling : CCS · 2023Article
- EPHB4-RASA1-Mediated Negative Regulation of Ras-MAPK Signaling in the Vasculature: Implications for the Treatment of EPHB4- and RASA1-Related Vascular Anomalies in Humans.Pharmaceuticals (Basel, Switzerland) · 2023Review
- RNA-seq co-expression network analysis reveals anxiolytic behavior of mice with Efnb2 knockout in parvalbumin+ neurons.Molecular brain · 2021Article
- EphrinB2-EphB2 signaling for dendrite protection after neuronal ischemiaJournal of cerebral blood flow and metabolism : official journal of the International Society of Cerebral Blood Flow and Metabolism · 2021Article
- Review
- Loss of tyrosine kinase receptor Ephb2 impairs proliferation and stem cell activity of spermatogonia in culture†.Biology of reproduction · 2020Article
- The Shb scaffold binds the Nck adaptor protein, p120 RasGAP, and Chimaerins and thereby facilitates heterotypic cell segregation by the receptor EphB2.The Journal of biological chemistry · 2020Article
- Phosphoproteomics identifies a bimodal EPHA2 receptor switch that promotes embryonic stem cell differentiation.Nature communications · 2020Article
- Heterotypic contact inhibition of locomotion can drive cell sorting between epithelial and mesenchymal cell populations.Journal of cell science · 2019Article
- Caught in the "Akt": Cross-talk between EphA2 and EGFR through the Akt-PIKfyve axis maintains cellular sensitivity to EGF.Science signaling · 2018Article
- Optogenetic activation of EphB2 receptor in dendrites induced actin polymerization by activating Arg kinase.Biology open · 2017Article
- Ubiquitin ligase SPSB4 diminishes cell repulsive responses mediated by EphB2.Molecular biology of the cell · 2017Article
- TNF-α/TNFR2 Regulatory Axis Stimulates EphB2-Mediated Neuroregeneration Via Activation of NF-κB.Journal of cellular physiology · 2016Article
- p120RasGAP Protein Mediates Netrin-1 Protein-induced Cortical Axon Outgrowth and Guidance.The Journal of biological chemistry · 2016Article
- Infralimbic EphB2 Modulates Fear Extinction in Adolescent Rats.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2015Article
- Knockdown of EphB1 receptor decreases medulloblastoma cell growth and migration and increases cellular radiosensitization.Oncotarget · 2015Article
13 more citing papers are in PubMed but not listed here.
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of the EphB2 receptor tyrosine kinase by clustered ephrin-B1 induces growth cone collapse and neurite retraction in differentiated NG108 neuronal cells. We have investigated the cytoplasmic signaling events associated with EphB2-induced cytoskeletal reorganization in these neuronal cells. We find that unlike other receptor tyrosine kinases, EphB2 induces a pronounced downregulation of GTP-bound Ras and consequently of the extracellular signal-regulated kinase (ERK) mitogen-activated protein kinase (MAPK) pathway. A similar inhibition of the Ras-MAPK pathway was observed on stimulation of endogenous EphB2 in COS-1 cells. Inactivation of Ras, induced by ephrin B1 stimulation of NG108 neuronal cells, requires EphB2 tyrosine kinase activity and is blocked by a truncated form of p120-Ras GTPase-activating protein (p120-RasGAP), suggesting that EphB2 signals through the SH2 domain protein p120-RasGAP to inhibit the Ras-MAPK pathway. Suppression of Ras activity appears functionally important, since expression of a constitutively active variant of Ras impaired the ability of EphB2 to induce neurite retraction. In addition, EphB2 attenuated the elevation in ERK activation induced by attachment of NG108 cells to fibronectin, indicating that the EphB2 receptor can modulate integrin signaling to the Ras GTPase. These results suggest that a primary function of EphB2, a member of the most populous family of receptor tyrosine kinases, is to inactivate the Ras-MAPK pathway in a fashion that contributes to cytoskeletal reorganization and adhesion responses in neuronal growth cones.
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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.