ArticleNPJ systems biology and applications2021
Predicted 'wiring landscape' of Ras-effector interactions in 29 human tissues.
Article in NPJ systems biology and applications, 2021. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 18 papers.
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Who cites it
18 citing papers in PubMed, 24 citations in OpenAlex.
- Revisiting RAS family GTPase signaling: effector selectivity and oncogenic bypass.The Biochemical journal · 2026Review
- KRAS: the Achilles' heel of pancreas cancer biology.The Journal of clinical investigation · 2025Review
- "Undruggable KRAS": druggable after all.Genes & development · 2025Review
- Functional and structural insights into RAS effector proteins.Molecular cell · 2024Review
- Determining the ERK-regulated phosphoproteome driving KRAS-mutant cancer.Science (New York, N.Y.) · 2024Article
- The Legionella pneumophila effector DenR hijacks the host NRas proto-oncoprotein to downregulate MAPK signaling.Cell reports · 2024Article
- Structural insights into the complex of oncogenic KRas4BLife science alliance · 2024Article
- K-RAS Is…Complicated.Cancers · 2023Article
- Direct Observation of Membrane-Associated H-Ras in the Native Cellular Environment by In-CellJACS Au · 2023Article
- Analysis of context-specific KRAS-effector (sub)complexes in Caco-2 cells.Life science alliance · 2023Article
- Dynamic regulation of RAS and RAS signaling.The Biochemical journal · 2023Article
- Article
- Pax3 loss of function delays tumour progression in kRAS-induced zebrafish rhabdomyosarcoma models.Scientific reports · 2022Article
- Identification of the gene expression changes and gene regulatory aspects in ELF3 mutant bladder cancer.Molecular biology reports · 2022Article
- Reconstruction and analysis of a large-scale binary Ras-effector signaling network.Cell communication and signaling : CCS · 2022Article
- Review
- Signaling pathways in intestinal homeostasis and colorectal cancer: KRAS at centre stage.Cell communication and signaling : CCS · 2021Review
- The Ins and Outs of RAS Effector Complexes.Biomolecules · 2021Review
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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
Ras is a plasma membrane (PM)-associated signaling hub protein that interacts with its partners (effectors) in a mutually exclusive fashion. We have shown earlier that competition for binding and hence the occurrence of specific binding events at a hub protein can modulate the activation of downstream pathways. Here, using a mechanistic modeling approach that incorporates high-quality proteomic data of Ras and 56 effectors in 29 (healthy) human tissues, we quantified the amount of individual Ras-effector complexes, and characterized the (stationary) Ras "wiring landscape" specific to each tissue. We identified nine effectors that are in significant amount in complex with Ras in at least one of the 29 tissues. We simulated both mutant- and stimulus-induced network re-configurations, and assessed their divergence from the reference scenario, specifically discussing a case study for two stimuli in three epithelial tissues. These analyses pointed to 32 effectors that are in significant amount in complex with Ras only if they are additionally recruited to the PM, e.g. via membrane-binding domains or domains binding to activated receptors at the PM. Altogether, our data emphasize the importance of tissue context for binding events at the Ras signaling hub.
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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.