ArticleNature cell biology2014
Protein interaction switches coordinate Raf-1 and MST2/Hippo signalling.
Article in Nature cell biology, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 99 papers.
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Who cites it
99 citing papers in PubMed, 150 citations in OpenAlex.
- EphA2 as an oncogenic driver: roles and mechanisms of action in cancer.Molecular biology reports · 2026Review
- The Hippo signaling pathway in pediatric brain tumors: molecular mechanisms and therapeutic opportunities.Cancer metastasis reviews · 2026Review
- A computational rule-based model of MAPK/ERK system regulation.Scientific reports · 2026Article
- PR55α subunit of protein phosphatase 2A supports KRASOncogene · 2025Article
- The antipsychotic drug pimozide promotes apoptosis through the RAF/ERK pathway and enhances autophagy in breast cancer cells.Cancer biology & therapy · 2024Article
- Rac1 GTPase Regulates the βTrCP-Mediated Proteolysis of YAP Independently of the LATS1/2 Kinases.Cancers · 2024Article
- Insights gained from computational modeling of YAP/TAZ signaling for cellular mechanotransduction.NPJ systems biology and applications · 2024Review
- STK3 kinase activation inhibits tumor proliferation through FOXO1-TP53INP1/P21 pathway in esophageal squamous cell carcinoma.Cellular oncology (Dordrecht, Netherlands) · 2024Article
- Review
- SIRT4 as a novel interactor and candidate suppressor of C-RAF kinase in MAPK signaling.Life science alliance · 2024Article
- Innate immune signal transduction pathways to fungal infection: Components and regulation.Cell insight · 2024Review
- Article
- Targeting CRAF kinase in anti-cancer therapy: progress and opportunities.Molecular cancer · 2023Review
- New Insights into YAP/TAZ-TEAD-Mediated Gene Regulation and Biological Processes in Cancer.Cancers · 2023Review
- Multi-Functional Regulation by YAP/TAZ Signaling Networks in Tumor Progression and Metastasis.Cancers · 2023Review
- Article
- Molecular and cellular evidence for the impact of a hypertrophic cardiomyopathy-associated RAF1 variant on the structure and function of contractile machinery in bioartificial cardiac tissues.Communications biology · 2023Article
- Analysis of context-specific KRAS-effector (sub)complexes in Caco-2 cells.Life science alliance · 2023Article
- The Hippo signaling pathway: from multiple signals to the hallmarks of cancers.Acta biochimica et biophysica Sinica · 2023Review
- Mechanisms underlying divergent relationships between CaThe Journal of physiology · 2023Article
39 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
7 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Signal transduction requires the coordination of activities between different pathways. In mammalian cells, Raf-1 regulates the MST-LATS and MEK-ERK pathways. We found that a complex circuitry of competing protein interactions coordinates the crosstalk between the ERK and MST pathways. Combining mathematical modelling and experimental validation we show that competing protein interactions can cause steep signalling switches through phosphorylation-induced changes in binding affinities. These include Akt phosphorylation of MST2 and a feedback phosphorylation of Raf-1 Ser 259 by LATS1, which enables Raf-1 to suppress both MST2 and MEK signalling. Mutation of Raf-1 Ser 259 stimulates both pathways, simultaneously driving apoptosis and proliferation, whereas concomitant MST2 downregulation switches signalling to cell proliferation, transformation and survival. Thus, competing protein interactions provide a versatile regulatory mechanism for signal distribution through the dynamic integration of graded signals into switch-like responses.
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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.