ArticleNature structural & molecular biology2022
Structure of the SHOC2-MRAS-PP1C complex provides insights into RAF activation and Noonan syndrome.
Article in Nature structural & molecular biology, 2022. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers, 1 of them a synthesis that pooled it.
What it found
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Who cites it
34 citing papers in PubMed, 1 synthesis or guideline pooled it, 51 citations in OpenAlex.
- Pooled it
- Targeting SHOC2: a treatable therapeutic site in RAS(Q61) mutant cancers.Science China. Life sciences · 2026Article
- Expression of LIFR in tumor and SHOC2, YAP1 in plasma mRNA as potential biomarkers in KRASScientific reports · 2026Article
- Revisiting RAS family GTPase signaling: effector selectivity and oncogenic bypass.The Biochemical journal · 2026Review
- Analysis of the Modulation of RAF Signaling by 14-3-3 Proteins.Bulletin of mathematical biology · 2026Article
- Positive cooperativity between RAS-binding and cysteine-rich domains regulates RAF membrane binding kinetics via lateral rebinding.Nature communications · 2026Article
- Structure of SHOC2-KRAS-PP1C complex reveals RAS isoform-specific determinants and insights into targeting complex assembly by RAS inhibitors.Nature communications · 2026Article
- An in vitro BRAF activation assay elucidates molecular mechanisms driving disassembly of the autoinhibited BRAF state.Proceedings of the National Academy of Sciences of the United States of America · 2025Article
- Tumor heterogeneity underlies clinical outcome and MEK inhibitor response in somatic NF1-mutant glioblastoma.JCI insight · 2025Article
- Structural basis for LZTR1 recognition of RAS GTPases for degradation.Science (New York, N.Y.) · 2025Article
- Cryo-EM structures of CRAF/MEK1/14-3-3 complexes in autoinhibited and open-monomer states reveal features of RAF regulation.Nature communications · 2025Article
- Article
- The small GTPase MRAS is a broken switch.Nature communications · 2025Article
- A New Dawn for Targeted Cancer Therapy: Small Molecule Covalent Binding Inhibitor Targeting K-Ras (G12C).Current medicinal chemistry · 2025Review
- M-Ras distinct activation scenarios: A mechanistic outlook and targeting.Computational and structural biotechnology journal · 2025Article
- Targeting KAT7 inhibits the progression of colorectal cancer.Theranostics · 2025Article
- The prominent pervasive oncogenic role and tissue specific permissiveness of RAS gene mutations.Scientific reports · 2024Article
- Variants in LRRC7 lead to intellectual disability, autism, aggression and abnormal eating behaviors.Nature communications · 2024Article
- The expression of congenital Shoc2 variants induces AKT-dependent crosstalk activation of the ERK1/2 pathway.Human molecular genetics · 2024Article
- Crystal structure of the GDP-bound human M-RAS protein in two crystal forms.Acta crystallographica. Section F, Structural biology communications · 2024Article
Corrections and comments
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Authors and funding
13 authors at 3 institutions in 2 countries.
Funding
Abstract
SHOC2 acts as a strong synthetic lethal interactor with MEK inhibitors in multiple KRAS cancer cell lines. SHOC2 forms a heterotrimeric complex with MRAS and PP1C that is essential for regulating RAF and MAPK-pathway activation by dephosphorylating a specific phosphoserine on RAF kinases. Here we present the high-resolution crystal structure of the SHOC2-MRAS-PP1C (SMP) complex and apo-SHOC2. Our structures reveal that SHOC2, MRAS, and PP1C form a stable ternary complex in which all three proteins synergistically interact with each other. Our results show that dephosphorylation of RAF substrates by PP1C is enhanced upon interacting with SHOC2 and MRAS. The SMP complex forms only when MRAS is in an active state and is dependent on SHOC2 functioning as a scaffolding protein in the complex by bringing PP1C and MRAS together. Our results provide structural insights into the role of the SMP complex in RAF activation and how mutations found in Noonan syndrome enhance complex formation, and reveal new avenues for therapeutic interventions.
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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.