ArticleMolecular and cellular biology2013
Extracellular signal-regulated kinase regulates RhoA activation and tumor cell plasticity by inhibiting guanine exchange factor H1 activity.
Article in Molecular and cellular biology, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 26 papers.
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Who cites it
26 citing papers in PubMed, 33 citations in OpenAlex.
- Mechanistic insights on spatiotemporal control of Ras-signaling.Biological chemistry · 2026Review
- Mechanism of ERK-mediated Rho Activation and Stress Fiber Assembly for Cell Migration.bioRxiv : the preprint server for biology · 2025Article
- Guanine Nucleotide Exchange Factors and Small GTPases: Their Regulation and Functions, Diseases, and Therapeutic Targets.MedComm · 2025Review
- Dynamic Coupling of MAPK Signaling to the Guanine Nucleotide Exchange Factor GEF-H1.OncoTargets and therapy · 2025Review
- Linear motif specificity in signaling through p38α and ERK2 mitogen-activated protein kinases.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- HUNK inhibits epithelial-mesenchymal transition of CRC via direct phosphorylation of GEF-H1 and activating RhoA/LIMK-1/CFL-1.Cell death & disease · 2023Article
- TMBIM6-mediated miR-181a expression regulates breast cancer cell migration and invasion via the MAPK/ERK signaling pathway.Journal of Cancer · 2023Article
- The Crossroads between RAS and RHO Signaling Pathways in Cellular Transformation, Motility and Contraction.Genes · 2021Review
- NEK9, a novel effector of IL-6/STAT3, regulates metastasis of gastric cancer by targeting ARHGEF2 phosphorylation.Theranostics · 2021Article
- The Inhibition of Wnt Restrain KRASCancers · 2020Article
- VE-PTP stabilizes VE-cadherin junctions and the endothelial barrier via a phosphatase-independent mechanism.The Journal of cell biology · 2019Article
- Integrin-uPAR signaling leads to FRA-1 phosphorylation and enhanced breast cancer invasion.Breast cancer research : BCR · 2018Article
- Quantitative Assessment of the Effects of Trypsin Digestion Methods on Affinity Purification-Mass Spectrometry-based Protein-Protein Interaction Analysis.Journal of proteome research · 2017Article
- Article
- Vimentin intermediate filaments control actin stress fiber assembly through GEF-H1 and RhoA.Journal of cell science · 2017Article
- A MAPK-Driven Feedback Loop Suppresses Rac Activity to Promote RhoA-Driven Cancer Cell Invasion.PLoS computational biology · 2016Article
- Bistability in the Rac1, PAK, and RhoA Signaling Network Drives Actin Cytoskeleton Dynamics and Cell Motility Switches.Cell systems · 2016Article
- Phosphorylation and Activation of RhoA by ERK in Response to Epidermal Growth Factor Stimulation.PloS one · 2016Article
- Guanine nucleotide exchange factor H1 can be a new biomarker of melanoma.Biologics : targets & therapy · 2016Article
- RalB regulates contractility-driven cancer dissemination upon TGFβ stimulation via the RhoGEF GEF-H1.Scientific reports · 2015Article
Corrections and comments
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Authors and funding
13 authors at 2 institutions in 3 countries.
Funding
Abstract
In certain Ras mutant cell lines, the inhibition of extracellular signal-regulated kinase (ERK) signaling increases RhoA activity and inhibits cell motility, which was attributed to a decrease in Fra-1 levels. Here we report a Fra-1-independent augmentation of RhoA signaling during short-term inhibition of ERK signaling. Using mass spectrometry-based proteomics, we identified guanine exchange factor H1 (GEF-H1) as mediating this effect. ERK binds to the Rho exchange factor GEF-H1 and phosphorylates it on S959, causing inhibition of GEF-H1 activity and a consequent decrease in RhoA activity. Knockdown experiments and expression of a nonphosphorylatable S959A GEF-H1 mutant showed that this site is crucial in regulating cell motility and invasiveness. Thus, we identified GEF-H1 as a critical ERK effector that regulates motility, cell morphology, and invasiveness.
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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.