ArticleThe Journal of biological chemistry2015
Anchoring of protein kinase A by ERM (ezrin-radixin-moesin) proteins is required for proper netrin signaling through DCC (deleted in colorectal cancer).
Article in The Journal of biological chemistry, 2015. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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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.
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Who cites it
20 citing papers in PubMed, 25 citations in OpenAlex.
- Regulation of Translation by PKA Signaling Pathway.International journal of molecular sciences · 2026Review
- Review
- The value and application of a poorly differentiated cluster-based Ezrin marginal score system in the prognostic assessment of colorectal cancer.Discover oncology · 2025Article
- Insights into the regulation of mRNA translation by scaffolding proteins.Biochemical Society transactions · 2024Review
- Emerging roles of prominin-1 (CD133) in the dynamics of plasma membrane architecture and cell signaling pathways in health and disease.Cellular & molecular biology letters · 2024Review
- Ezrin Contributes to the Damage of Airway Epithelial Barrier Related to Diabetes Mellitus.Journal of inflammation research · 2024Article
- Cytoskeletal and Cytoskeleton-Associated Proteins: Key Regulators of Cancer Stem Cell Properties.Pharmaceuticals (Basel, Switzerland) · 2022Review
- Pathophysiological Roles of Actin-Binding Scaffold Protein, Ezrin.International journal of molecular sciences · 2022Review
- Protein Kinase A in cellular migration-Niche signaling of a ubiquitous kinase.Frontiers in molecular biosciences · 2022Review
- Prominin-1-Radixin axis controls hepatic gluconeogenesis by regulating PKA activity.EMBO reports · 2020Article
- Characterizing lineage-specific evolution and the processes driving genomic diversification in chordates.BMC evolutionary biology · 2020Article
- Protein kinase A activity is regulated by actomyosin contractility during cell migration and is required for durotaxis.Molecular biology of the cell · 2020Article
- A PKA/cdc42 Signaling Axis Restricts Angiogenic Sprouting by Regulating Podosome Rosette Biogenesis and Matrix Remodeling.Scientific reports · 2019Article
- Ezrin, a Membrane Cytoskeleton Cross-Linker Protein, as a Marker of Epithelial Damage in Asthma.American journal of respiratory and critical care medicine · 2019Article
- Intravital imaging reveals systemic ezrin inhibition impedes cancer cell migration and lymph node metastasis in breast cancer.Breast cancer research : BCR · 2019Article
- Mechanisms Underlying the Regulation of HP1γ by the NGF-PKA Signaling Pathway.Scientific reports · 2018Article
- Revisiting Netrin-1: One Who Guides (Axons).Frontiers in cellular neuroscience · 2018Review
- AKAP-mediated feedback control of cAMP gradients in developing hippocampal neurons.Nature chemical biology · 2017Article
- DLC-1 is an independent prognostic marker and potential therapeutic target in hepatocellular cancer.Diagnostic pathology · 2016Article
- Ezrin Orchestrates Signal Transduction in Airway Cells.Reviews of physiology, biochemistry and pharmacologyReview
Corrections and comments
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Authors and funding
6 authors at 2 institutions in 2 countries.
Funding
Abstract
Netrin-1, acting through its principal receptor DCC (deleted in colorectal cancer), serves as an axon guidance cue during neural development and also contributes to vascular morphogenesis, epithelial migration, and the pathogenesis of some tumors. Several lines of evidence suggest that netrin-DCC signaling can regulate and be regulated by the cAMP-dependent protein kinase, PKA, although the molecular details of this relationship are poorly understood. Specificity in PKA signaling is often achieved through differential subcellular localization of the enzyme by interaction with protein kinase A anchoring proteins (AKAPs). Here, we show that AKAP function is required for DCC-mediated activation of PKA and phosphorylation of cytoskeletal regulatory proteins of the Mena/VASP (vasodilator-stimulated phosphoprotein) family. Moreover, we show that DCC and PKA physically interact and that this association is mediated by the ezrin-radixin-moesin (ERM) family of plasma membrane-actin cytoskeleton cross-linking proteins. Silencing of ERM protein expression inhibits DCC-PKA interaction, DCC-mediated PKA activation, and phosphorylation of Mena/VASP proteins as well as growth cone morphology and neurite outgrowth. Finally, although expression of wild-type radixin partially rescued growth cone morphology and tropism toward netrin in ERM-knockdown cells, expression of an AKAP-deficient mutant of radixin did not fully rescue growth cone morphology and switched netrin tropism from attraction to repulsion. These data support a model in which ERM-mediated anchoring of PKA activity to DCC is required for proper netrin/DCC-mediated signaling.
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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.