ArticleThe Journal of neuroscience : the official journal of the Society for Neuroscience2009
Inactivation of Ras by p120GAP via focal adhesion kinase dephosphorylation mediates RGMa-induced growth cone collapse.
Article in The Journal of neuroscience : the official journal of the Society for Neuroscience, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 35 papers.
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Who cites it
35 citing papers in PubMed, 47 citations in OpenAlex.
- Cross-species functional analysis of aResearch square · 2026Article
- Molecular resilience of neurons to repetitive mechanical compression.Communications biology · 2026Article
- Unlocking the Therapeutic Potential of RGMa: A New Frontier in Neurological Disorder Treatment.Molecular neurobiology · 2025Review
- Integration of scRNA-seq and bulk tissue RNA-seq data to identify cancer-associated fibroblast-related gene RGMA as a potential treatment target for esophageal cancer.Functional & integrative genomics · 2025Article
- Identification of SH2 Domain-Containing Protein 3C as a Novel, Putative Interactor of Dipeptidyl Peptidase 3.International journal of molecular sciences · 2023Article
- Role of nerves in neurofibromatosis type 1-related nervous system tumors.Cellular oncology (Dordrecht, Netherlands) · 2022Review
- Aberrant promoter hypermethylation inhibits RGMA expression and contributes to tumor progression in breast cancer.Oncogene · 2022Article
- The roles of GTPase-activating proteins in regulated cell death and tumor immunity.Journal of hematology & oncology · 2021Review
- MiR-552-3p promotes malignant progression of gallbladder carcinoma by reactivating the Akt/β-catenin signaling pathway due to inhibition of the tumor suppressor geneAnnals of translational medicine · 2021Article
- Inhibition of repulsive guidance molecule-a protects dopaminergic neurons in a mouse model of Parkinson's disease.Cell death & disease · 2021Article
- Review
- Repulsive Guidance Molecule A Suppresses Adult Neurogenesis.Stem cell reports · 2020Article
- Glial Cell-Axonal Growth Cone Interactions in Neurodevelopment and Regeneration.Frontiers in neuroscience · 2020Review
- Review
- RGMa mediates reactive astrogliosis and glial scar formation through TGFβ1/Smad2/3 signaling after stroke.Cell death and differentiation · 2018Article
- Repulsive Guidance Molecule a (RGMa) Induces Neuropathological and Behavioral Changes That Closely Resemble Parkinson's Disease.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2017Article
- Annexin A6-A multifunctional scaffold in cell motility.Cell adhesion & migration · 2017Review
- RGMs: Structural Insights, Molecular Regulation, and Downstream Signaling.Trends in cell biology · 2017Review
- Minocycline Promotes Neurite Outgrowth of PC12 Cells Exposed to Oxygen-Glucose Deprivation and Reoxygenation Through Regulation of MLCP/MLC Signaling Pathways.Cellular and molecular neurobiology · 2017Article
- p120RasGAP Protein Mediates Netrin-1 Protein-induced Cortical Axon Outgrowth and Guidance.The Journal of biological chemistry · 2016Article
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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
The repulsive guidance molecule RGMa performs several functions in the developing and adult CNSs. RGMa, through its receptor neogenin, induces growth cone collapse and neurite outgrowth inhibition. Here, we demonstrate that RGMa binding to neogenin leads to the inactivation of Ras, which is required for the RGMa-mediated repulsive function in cortical neurons. This signal transduction is mediated by the Ras-specific GTPase-activating protein (GAP) p120GAP. The SH2 domain of p120GAP interacts with focal adhesion kinase (FAK), which is phosphorylated at Tyr-397. When the cells are stimulated with RGMa, FAK undergoes dephosphorylation at Tyr-397 and is dissociated from p120GAP, and this dissociation is followed by an increase in the interaction between p120GAP and GTP-Ras. In addition, the knockdown of p120GAP prevents RGMa-induced growth cone collapse and neurite outgrowth inhibition. Furthermore, RGMa stimulation induces Akt inactivation through p120GAP, and the expression of the constitutively active Akt prevents RGMa-induced growth cone collapse. Thus, RGMa binding to neogenin regulates p120GAP activity through FAK Tyr-397 dephosphorylation, leading to the inactivation of Ras and its downstream effector Akt, and this signal transduction plays a role in the RGMa-mediated repulsive function.
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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.