ArticleThe Journal of cell biology2004
Localized Ras signaling at the leading edge regulates PI3K, cell polarity, and directional cell movement.
Article in The Journal of cell biology, 2004. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 237 papers, 1 of them a synthesis that pooled it.
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Who cites it
237 citing papers in PubMed, 1 synthesis or guideline pooled it, 372 citations in OpenAlex.
- A meta-analysis indicates that the regulation of cell motility is a non-intrinsic function of chemoattractant receptors that is governed independently of directional sensing.Frontiers in immunology · 2022Pooled it
- A chemigenetic endogenous Ras activity biosensor for live-cell pharmacology.Nature chemical biology · 2026Article
- PIP5K-Ras bistability triggers plasma membrane symmetry breaking to define cellular polarity and regulate migration.Nature communications · 2026Article
- Loss of Copine D Leads to Ras Activation inCells · 2026Article
- Reconstitution of Ras-PI3Kγ membrane communication and feedback using light-induced signaling inputs.Nature communications · 2026Article
- Article
- Loss of Copine D Leads to Ras Activation inbioRxiv : the preprint server for biology · 2026Article
- Local Ras/actin signaling orients individual pseudopods in shallow gradients.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- A computational rule-based model of MAPK/ERK system regulation.Scientific reports · 2026Article
- PIP5K-Ras bistability triggers plasma membrane symmetry breaking to define cellular polarity and regulate migration.bioRxiv : the preprint server for biology · 2025Article
- Rax1/2 promote memory of growth by early Ras1 activation to maintain polarity across generations.bioRxiv : the preprint server for biology · 2025Article
- Spatial distribution of cytoskeleton-mediated feedback controls cell polarization: A computational study.PLoS computational biology · 2025Article
- Supersulfides regulate cell migration in human skin keratinocytes.Cell structure and function · 2025Article
- Signaling and actin waves at a glance.Journal of cell science · 2025Review
- Complementary cytoskeletal feedback loops control signal transduction excitability and cell polarity.Nature communications · 2025Article
- Front-biased activation of the Ras-Rab5-Rac1 loop coordinates collective cell migration.Journal of cell science · 2025Article
- Filopodia numbers impact chemotactic migration speed.bioRxiv : the preprint server for biology · 2025Article
- Spatial distribution of cytoskeleton-mediated feedback controls cell polarization: a computational study.bioRxiv : the preprint server for biology · 2025Article
- Unravelling molecular dynamics in living cells: Fluorescent protein biosensors for cell biology.Journal of microscopy · 2025Review
- Excitable Ras dynamics-based screens reveal RasGEFX is required for macropinocytosis and random cell migration.Nature communications · 2025Article
177 more citing papers are in PubMed but not listed here.
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
4 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
During chemotaxis, receptors and heterotrimeric G-protein subunits are distributed and activated almost uniformly along the cell membrane, whereas PI(3,4,5)P(3), the product of phosphatidylinositol 3-kinase (PI3K), accumulates locally at the leading edge. The key intermediate event that creates this strong PI(3,4,5)P(3) asymmetry remains unclear. Here, we show that Ras is rapidly and transiently activated in response to chemoattractant stimulation and regulates PI3K activity. Ras activation occurs at the leading edge of chemotaxing cells, and this local activation is independent of the F-actin cytoskeleton, whereas PI3K localization is dependent on F-actin polymerization. Inhibition of Ras results in severe defects in directional movement, indicating that Ras is an upstream component of the cell's compass. These results support a mechanism by which localized Ras activation mediates leading edge formation through activation of basal PI3K present on the plasma membrane and other Ras effectors required for chemotaxis. A feedback loop, mediated through localized F-actin polymerization, recruits cytosolic PI3K to the leading edge to amplify the signal.
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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.