ArticleThe EMBO journal2003
Mechanism of the spatio-temporal regulation of Ras and Rap1.
Article in The EMBO journal, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 50 papers.
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Who cites it
50 citing papers in PubMed, 109 citations in OpenAlex.
- Functional characterization of the 9q34.13 locus identifies RAPGEF1 as a candidate gene modulating risk for melanoma and nevi via RAS activation.American journal of human genetics · 2026Article
- Functional characterization of the 9q34.13 locus identifiesbioRxiv : the preprint server for biology · 2026Article
- Metabolic Responses to Cyclic Fasting in Juvenile Turbot (Aquaculture nutrition · 2026Article
- EGFR-dependent actomyosin patterning coordinates morphogenetic movements between tissues in Drosophila melanogaster.Developmental cell · 2025Article
- EGFR-dependent actomyosin patterning coordinates morphogenetic movements between tissues.bioRxiv : the preprint server for biology · 2023Article
- Ubiquitylation by Rab40b/Cul5 regulates Rap2 localization and activity during cell migration.The Journal of cell biology · 2022Article
- Identification of phenotype-specific networks from paired gene expression-cell shape imaging data.Genome research · 2022Article
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- The road to ERK activation: Do neurons take alternate routes?Cellular signalling · 2020Review
- A Peptide Derived from Phosphoinositide 3-kinase Inhibits Endocytosis and Influenza Virus Infection.Cell structure and function · 2019Article
- Modifying Rap1-signalling by targeting Pde6δ is neuroprotective in models of Alzheimer's disease.Molecular neurodegeneration · 2018Article
- Developmental stage-dependent regulation of spine formation by calcium-calmodulin-dependent protein kinase IIα and Rap1.Scientific reports · 2017Article
- SHANK proteins limit integrin activation by directly interacting with Rap1 and R-Ras.Nature cell biology · 2017Article
- Beta-Adrenoceptor Activation Reduces Both Dermal Microvascular Endothelial Cell Migration via a cAMP-Dependent Mechanism and Wound Angiogenesis.Journal of cellular physiology · 2015Article
- Targeted activation of conventional and novel protein kinases C through differential translocation patterns.Molecular and cellular biology · 2014Article
- Rasip1 mediates Rap1 regulation of Rho in endothelial barrier function through ArhGAP29.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Article
- Plexins are GTPase-activating proteins for Rap and are activated by induced dimerization.Science signaling · 2012Article
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- Nras overexpression results in granulocytosis, T-cell expansion and early lethality in mice.PloS one · 2012Article
Corrections and comments
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Epidermal growth factor (EGF) activates Ras and Rap1 at distinct intracellular regions. Here, we explored the mechanism underlying this phenomenon. We originally noticed that in cells expressing Epac, a cAMP-dependent Rap1 GEF (guanine nucleotide exchange factor), cAMP activated Rap1 at the perinuclear region, as did EGF. However, in cells expressing e-GRF, a recombinant cAMP-responsive Ras GEF, cAMP activated Ras at the peripheral plasma membrane. Based on the uniform cytoplasmic expression of Epac and e-GRF, GEF did not appear to account for the non-uniform increase in the activities of Ras and Rap1. In contrast, when we used probes with reduced sensitivity to GTPase-activating proteins (GAPs), both Ras and Rap1 appeared to be activated uniformly in the EGF-stimulated cells. Furthermore, we calculated the local rate constants of GEFs and GAPs from the video images of Ras activation and found that GAP activity was higher at the central plasma membrane than the periphery. Thus we propose that GAP primarily dictates the spatial regulation of Ras family G proteins, whereas GEF primarily determines the timing of Ras activation.
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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.