ArticleCell reports2020
Structural Insights into the SPRED1-Neurofibromin-KRAS Complex and Disruption of SPRED1-Neurofibromin Interaction by Oncogenic EGFR.
Article in Cell reports, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 42 papers.
What it found
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
The trial behind it
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
42 citing papers in PubMed, 69 citations in OpenAlex.
- Investigating the effects of missense mutations on the dual Ras/Rap activation mechanism of SYNGAP1 using molecular modelling.Journal of structural biology: X · 2026Article
- GDP-Loaded K-Ras Transiently Binds to Effector B-Raf RBD, Mirroring the Structure of the Active GTP-Loaded Complex.Journal of the American Chemical Society · 2026Article
- Context-dependent selection sculpts mutational landscapes in the normal lung.Research square · 2026Article
- Pathogenic Neurofibromatosis type 1 gene variants in tumors of non-NF1 patients and role of R1276.FEBS open bio · 2026Article
- Structure of SHOC2-KRAS-PP1C complex reveals RAS isoform-specific determinants and insights into targeting complex assembly by RAS inhibitors.Nature communications · 2026Article
- Review
- The impact of RAS on cell differentiation in health and disease.The Biochemical journal · 2025Review
- Structural determination of small proteins by cryo-EM using a coiled coil module strategy.Scientific reports · 2025Article
- Neurofibromin Encoded by theInternational journal of molecular sciences · 2025Article
- The role of SPRED1 mutation in melanoma.European journal of medical research · 2025Review
- Plasma membrane-associated ARAF condensates fuel RAS-related cancer drug resistance.Nature chemical biology · 2025Article
- Molecular Dynamics Simulations of the SPRED2International journal of molecular sciences · 2025Article
- Allosteric modulation of NF1 GAP: Differential distributions of catalytically competent populations in loss-of-function and gain-of-function mutants.Protein science : a publication of the Protein Society · 2025Article
- Biomarker Landscape in RASopathies.International journal of molecular sciences · 2024Review
- A Novel Homozygous Loss-of-Function Variant inGenes · 2023Article
- Structural and functional complexity of HSP90 in cellular homeostasis and disease.Nature reviews. Molecular cell biology · 2023Review
- RAS Signaling Gone Awry in the Skin: The Complex Role of RAS in Cutaneous Neurofibroma Pathogenesis, Emerging Biological Insights.The Journal of investigative dermatology · 2023Review
- The therapeutic potential of neurofibromin signaling pathways and binding partners.Communications biology · 2023Review
- Functional Assays Combined with Pre-mRNA-Splicing Analysis Improve Variant Classification and Diagnostics for Individuals with Neurofibromatosis Type 1 and Legius Syndrome.Human mutation · 2023Article
- The molecular genetics of RASopathies: An update on novel disease genes and new disorders.American journal of medical genetics. Part C, Seminars in medical genetics · 2022Review
Corrections and comments
PubMed lists nothing against this paper. Absence here is not a guarantee, only a check that was made.
Authors and funding
10 authors at 3 institutions in 2 countries.
Funding
Abstract
Sprouty-related, EVH1 domain-containing (SPRED) proteins negatively regulate RAS/mitogen-activated protein kinase (MAPK) signaling following growth factor stimulation. This inhibition of RAS is thought to occur primarily through SPRED1 binding and recruitment of neurofibromin, a RasGAP, to the plasma membrane. Here, we report the structure of neurofibromin (GTPase-activating protein [GAP]-related domain) complexed with SPRED1 (EVH1 domain) and KRAS. The structure provides insight into how the membrane targeting of neurofibromin by SPRED1 allows simultaneous interaction with activated KRAS. SPRED1 and NF1 loss-of-function mutations occur across multiple cancer types and developmental diseases. Analysis of the neurofibromin-SPRED1 interface provides a rationale for mutations observed in Legius syndrome and suggests why SPRED1 can bind to neurofibromin but no other RasGAPs. We show that oncogenic EGFR(L858R) signaling leads to the phosphorylation of SPRED1 on serine 105, disrupting the SPRED1-neurofibromin complex. The structural, biochemical, and biological results provide new mechanistic insights about how SPRED1 interacts with neurofibromin and regulates active KRAS levels in normal and pathologic conditions.
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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.