ArticleNature2001
The SH2/SH3 adaptor Grb4 transduces B-ephrin reverse signals.
Article in Nature, 2001. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 137 papers.
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Who cites it
137 citing papers in PubMed.
- The Role of Eph/Ephrin-Driven Actomyosin Contractility in Promoting Cell Segregation and Boundary Formation.International journal of molecular sciences · 2026Review
- The Eph-ephrin system in neuropsychiatric and neurodevelopmental disorders.Journal of psychiatry & neuroscience : JPN · 2026Review
- The role of lncRNAs in the interplay of signaling pathways and epigenetic mechanisms in glioma.Epigenomics · 2025Review
- EphB2 Receptor Promotes Dermal Fibrosis in Systemic Sclerosis.Arthritis & rheumatology (Hoboken, N.J.) · 2024Article
- Inhibition of Ephrin B2 Reverse Signaling Abolishes Multiple Myeloma Pathogenesis.Cancer research · 2024Article
- Functional Profiling of Soft Tissue Sarcoma Using Mechanistic Models.International journal of molecular sciences · 2023Article
- Review
- NCK1 Modulates Neuronal Actin Dynamics and Promotes Dendritic Spine, Synapse, and Memory Formation.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2023Article
- The relative binding position of Nck and Grb2 adaptors impacts actin-based motility of Vaccinia virus.eLife · 2022Article
- The Roles of EphB2 in Cancer.Frontiers in cell and developmental biology · 2022Review
- The Ephb2 Receptor Uses Homotypic, Head-to-Tail Interactions within Its Ectodomain as an Autoinhibitory Control Mechanism.International journal of molecular sciences · 2021Article
- Nck adaptors at a glance.Journal of cell science · 2021Article
- Natural loss of function of ephrin-B3 shapes spinal flight circuitry in birds.Science advances · 2021Article
- Paxillin Is Required for Proper Spinal Motor Axon Growth into the Limb.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2021Article
- Barcoded viral tracing of single-cell interactions in central nervous system inflammation.Science (New York, N.Y.) · 2021Article
- Eph-Ephrin Signaling Mediates Cross-Talk Within the Bone Microenvironment.Frontiers in cell and developmental biology · 2021Review
- Harnessing the Power of Eph/ephrin Biosemiotics for Theranostic Applications.Pharmaceuticals (Basel, Switzerland) · 2020Review
- The critical role of the interplays of EphrinB2/EphB4 and VEGF in the induction of angiogenesis.Molecular biology reports · 2020Review
- Axin Family of Scaffolding Proteins in Development: Lessons fromJournal of developmental biology · 2019Review
- Gulp1 controls Eph/ephrin trogocytosis and is important for cell rearrangements during development.The Journal of cell biology · 2019Article
77 more citing papers are in PubMed but not listed here.
Corrections and comments
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Authors and funding
2 authors.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Bidirectional signals mediated by membrane-anchored ephrins and Eph receptor tyrosine kinases have important functions in cell-cell recognition events, including those that occur during axon pathfinding and hindbrain segmentation. The reverse signal that is transduced into B-ephrin-expressing cells is thought to involve tyrosine phosphorylation of the signal's short, conserved carboxy-terminal cytoplasmic domain. The Src-homology-2 (SH2) domain proteins that associate with activated tyrosine-phosphorylated B-subclass ephrins have not been identified, nor has a defined cellular response to reverse signals been described. Here we show that the SH2/SH3 domain adaptor protein Grb4 binds to the cytoplasmic domain of B ephrins in a phosphotyrosine-dependent manner. In response to B-ephrin reverse signalling, cells increase FAK catalytic activity, redistribute paxillin, lose focal adhesions, round up, and disassemble F-actin-containing stress fibres. These cellular responses can be blocked in a dominant-negative fashion by expression of the isolated Grb4 SH2 domain. The Grb4 SH3 domains bind a unique set of other proteins that are implicated in cytoskeletal regulation, including the Cbl-associated protein (CAP/ponsin), the Abl-interacting protein-1 (Abi-1), dynamin, PAK1, hnRNPK and axin. These data provide a biochemical pathway whereby cytoskeletal regulators are recruited to Eph-ephrin bidirectional signalling complexes.
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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.