ArticleMolecular and cellular biology2001
The EphA8 receptor regulates integrin activity through p110gamma phosphatidylinositol-3 kinase in a tyrosine kinase activity-independent manner.
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 38 papers.
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Who cites it
38 citing papers in PubMed, 93 citations in OpenAlex.
- Roles of Eph-Ephrin Signaling in the Eye Lens Cataractogenesis, Biomechanics, and Homeostasis.Frontiers in cell and developmental biology · 2022Review
- Emerging Kinase Therapeutic Targets in Pancreatic Ductal Adenocarcinoma and Pancreatic Cancer Desmoplasia.International journal of molecular sciences · 2020Review
- Inhibition of EphB4-Ephrin-B2 Signaling Reprograms the Tumor Immune Microenvironment in Head and Neck Cancers.Cancer research · 2019Article
- Quantitative Proteomic Analysis of Small and Large Extracellular Vesicles (EVs) Reveals Enrichment of Adhesion Proteins in Small EVs.Journal of proteome research · 2019Article
- High Expression of EphA4 Predicted Lesser Degree of Tumor Regression after Neoadjuvant Chemoradiotherapy in Rectal Cancer.Journal of Cancer · 2017Article
- The oncocytic subtype is genetically distinct from other pancreatic intraductal papillary mucinous neoplasm subtypes.Modern pathology : an official journal of the United States and Canadian Academy of Pathology, Inc · 2016Article
- EphA8 is a prognostic marker for epithelial ovarian cancer.Oncotarget · 2016Article
- Dexamethasone Regulates EphA5, a Potential Inhibitory Factor with Osteogenic Capability of Human Bone Marrow Stromal Cells.Stem cells international · 2016Article
- Ephrin Ligands and Eph Receptors Show Regionally Restricted Expression in the Developing Palate and Tongue.Frontiers in physiology · 2016Article
- EphrinB1 expression is dysregulated and promotes oncogenic signaling in medulloblastoma.Journal of neuro-oncology · 2015Article
- EphA2 promotes cell adhesion and spreading of monocyte and monocyte/macrophage cell lines on integrin ligand-coated surfaces.Cell adhesion & migration · 2015Article
- Therapeutic targeting of EPH receptors and their ligands.Nature reviews. Drug discovery · 2014Review
- Mechanisms of ephrin receptor protein kinase-independent signaling in amphid axon guidance in Caenorhabditis elegans.Genetics · 2013Article
- EphB and Ephrin-B interactions mediate human mesenchymal stem cell suppression of activated T-cells.Stem cells and development · 2013Article
- Eph receptors and ephrins as targets for cancer therapy.Journal of cellular and molecular medicine · 2012Review
- Eph receptor signaling in C. elegans.WormBook : the online review of C. elegans biology · 2012Review
- Eph-dependent cell-cell adhesion and segregation in development and cancer.Cellular and molecular life sciences : CMLS · 2012Review
- EphA receptor signaling--complexity and emerging themes.Seminars in cell & developmental biology · 2012Review
- Luteolin decreases IGF-II production and downregulates insulin-like growth factor-I receptor signaling in HT-29 human colon cancer cells.BMC gastroenterology · 2012Article
- Eph/ephrin signaling in cell-cell and cell-substrate adhesion.Frontiers in bioscience (Landmark edition) · 2012Review
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Recent genetic studies suggest that ephrins may function in a kinase-independent Eph receptor pathway. Here we report that expression of EphA8 in either NIH 3T3 or HEK293 cells enhanced cell adhesion to fibronectin via alpha(5)beta(1)- or beta(3) integrins. Interestingly, a kinase-inactive EphA8 mutant also markedly promoted cell attachment to fibronectin in these cell lines. Using a panel of EphA8 point mutants, we have demonstrated that EphA8 kinase activity does not correlate with its ability to promote cell attachment to fibronectin. Analysis using EphA8 extracellular and intracellular domain mutants has revealed that enhanced cell adhesion is dependent on ephrin A binding to the extracellular domain and the juxtamembrane segment of the cytoplasmic domain of the receptor. EphA8-promoted adhesion was efficiently inhibited by wortmannin, a phosphatidylinositol 3-kinase (PI 3-kinase) inhibitor. Additionally, we found that EphA8 had associated PI 3-kinase activity and that the p110gamma isoform of PI 3-kinase is associated with EphA8. In vitro binding experiments revealed that the EphA8 juxtamembrane segment was sufficient for the formation of a stable complex with p110gamma. Similar results were obtained in assay using cells stripped of endogenous ephrin A ligands by treatment with preclustered ephrin A5-Fc proteins. In addition, a membrane-targeted lipid kinase-inactive p110gamma mutant was demonstrated to stably associate with EphA8 and suppress EphA8-promoted cell adhesion to fibronectin. Taken together, these results suggest the presence of a novel mechanism by which the EphA8 receptor localizes p110gamma PI 3-kinase to the plasma membrane in a tyrosine kinase-independent fashion, thereby allowing access to lipid substrates to enable the signals required for integrin-mediated cell adhesion.
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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.