ArticleThe Journal of cell biology2009
From autoinhibition to inhibition in trans: the Raf-1 regulatory domain inhibits Rok-alpha kinase activity.
Article in The Journal of cell biology, 2009. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
What it found
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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
32 citing papers in PubMed, 53 citations in OpenAlex.
- A computational rule-based model of MAPK/ERK system regulation.Scientific reports · 2026Article
- Challenging AlphaFold in predicting proteins with large-scale allosteric transitions.Communications chemistry · 2025Article
- Disruption of the pro-oncogenic c-RAF-PDE8A complex represents a differentiated approach to treating KRAS-c-RAF dependent PDAC.Scientific reports · 2024Article
- Targeting CRAF kinase in anti-cancer therapy: progress and opportunities.Molecular cancer · 2023Review
- Targeting the RAS/RAF/MAPK pathway for cancer therapy: from mechanism to clinical studies.Signal transduction and targeted therapy · 2023Review
- OTUD7B Activates Wnt Signaling Pathway through the Interaction with LEF1.Biomolecules · 2023Article
- MITF activity is regulated by a direct interaction with RAF proteins in melanoma cells.Communications biology · 2022Article
- The Crossroads between RAS and RHO Signaling Pathways in Cellular Transformation, Motility and Contraction.Genes · 2021Review
- Review
- Ras acts as a molecular switch between two forms of consolidated memory inProceedings of the National Academy of Sciences of the United States of America · 2020Article
- Review
- ROCK1 and 2 differentially regulate actomyosin organization to drive cell and synaptic polarity.The Journal of cell biology · 2015Article
- Activation of RAF1 (c-RAF) by the Marine Alkaloid Lasonolide A Induces Rapid Premature Chromosome Condensation.Marine drugs · 2015Article
- "RAF" neighborhood: protein-protein interaction in the Raf/Mek/Erk pathway.FEBS letters · 2014Article
- Mammalian STE20-like kinase 2, not kinase 1, mediates photoreceptor cell death during retinal detachment.Cell death & disease · 2014Article
- Phosphorylation and mRNA splicing of collapsin response mediator protein-2 determine inhibition of rho-associated protein kinase (ROCK) II function in carcinoma cell migration and invasion.The Journal of biological chemistry · 2013Article
- EGFR-ras-raf signaling in epidermal stem cells: roles in hair follicle development, regeneration, tissue remodeling and epidermal cancers.International journal of molecular sciences · 2013Review
- Regulation of ROCK activity in cancer.The journal of histochemistry and cytochemistry : official journal of the Histochemistry Society · 2013Review
- Protein kinases of the Hippo pathway: regulation and substrates.Seminars in cell & developmental biology · 2012Review
- The intermediate-activity (L597V)BRAF mutant acts as an epistatic modifier of oncogenic RAS by enhancing signaling through the RAF/MEK/ERK pathway.Genes & development · 2012Article
Corrections and comments
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Authors and funding
14 authors at 5 institutions in 5 countries.
Funding
Abstract
The activity of Raf-1 and Rok-alpha kinases is regulated by intramolecular binding of the regulatory region to the kinase domain. Autoinhibition is relieved upon binding to the small guanosine triphosphatases Ras and Rho. Downstream of Ras, Raf-1 promotes migration and tumorigenesis by antagonizing Rok-alpha, but the underlying mechanism is unknown. In this study, we show that Rok-alpha inhibition by Raf-1 relies on an intermolecular interaction between the Rok-alpha kinase domain and the cysteine-rich Raf-1 regulatory domain (Raf-1reg), which is similar to Rok-alpha's own autoinhibitory region. Thus, Raf-1 mediates Rok-alpha inhibition in trans, which is a new concept in kinase regulation. This mechanism is physiologically relevant because Raf-1reg is sufficient to rescue all Rok-alpha-dependent defects of Raf-1-deficient cells. Downstream of Ras and Rho, the Raf-1-Rok-alpha interaction represents a novel paradigm of pathway cross talk that contributes to tumorigenesis and cell motility.
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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.