ArticleMolecular and cellular biochemistry1999
Mutational analysis of Raf-1 cysteine rich domain: requirement for a cluster of basic aminoacids for interaction with phosphatidylserine.
Article in Molecular and cellular biochemistry, 1999. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 64 citations in OpenAlex.
- DA-Raf synergistically binds to the plasma membrane and Ras to suppress ERK signaling.Life science alliance · 2025Article
- Insight into molecular basis and dynamics of full-length CRaf kinase in cellular signaling mechanisms.Biophysical journal · 2024Article
- Protein conformational ensembles in function: roles and mechanisms.RSC chemical biology · 2023Review
- Cryo-EM structure of a RAS/RAF recruitment complex.Nature communications · 2023Article
- Metabolomics Approach Reveals Important Glioblastoma Plasma Biomarkers for Tumor Biology.International journal of molecular sciences · 2023Article
- RASopathy mutations provide functional insight into the BRAF cysteine-rich domain and reveal the importance of autoinhibition in BRAF regulation.Molecular cell · 2022Article
- Allostery: Allosteric Cancer Drivers and Innovative Allosteric Drugs.Journal of molecular biology · 2022Review
- The mechanism of activation of MEK1 by B-Raf and KSR1.Cellular and molecular life sciences : CMLS · 2022Article
- The mechanism of Raf activation through dimerization.Chemical science · 2021Article
- Crystal Structure Reveals the Full Ras-Raf Interface and Advances Mechanistic Understanding of Raf Activation.Biomolecules · 2021Article
- B-Raf autoinhibition in the presence and absence of 14-3-3.Structure (London, England : 1993) · 2021Article
- KRAS interaction with RAF1 RAS-binding domain and cysteine-rich domain provides insights into RAS-mediated RAF activation.Nature communications · 2021Article
- The mechanism of activation of monomeric B-Raf V600E.Computational and structural biotechnology journal · 2021Article
- Multivalent assembly of KRAS with the RAS-binding and cysteine-rich domains of CRAF on the membrane.Proceedings of the National Academy of Sciences of the United States of America · 2020Article
- The quaternary assembly of KRas4B with Raf-1 at the membrane.Computational and structural biotechnology journal · 2020Article
- Article
- Does Ras Activate Raf and PI3K Allosterically?Frontiers in oncology · 2019Review
- Autoinhibition in Ras effectors Raf, PI3Kα, and RASSF5: a comprehensive review underscoring the challenges in pharmacological intervention.Biophysical reviews · 2018Review
- Raf-1 Cysteine-Rich Domain Increases the Affinity of K-Ras/Raf at the Membrane, Promoting MAPK Signaling.Structure (London, England : 1993) · 2018Article
- A "Tug of War" Maintains a Dynamic Protein-Membrane Complex: Molecular Dynamics Simulations of C-Raf RBD-CRD Bound to K-Ras4B at an Anionic Membrane.ACS central science · 2018Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Activation of Raf-1 kinase is preceded by a translocation of Raf-1 to the plasma membrane in response to external stimuli. The membrane localization of Raf-1 is facilitated through its interaction with activated Ras and with membrane phospholipids. Previous evidence suggests that the interaction of Raf-1 with Ras is mediated by two distinct domains within the N-terminal region of Raf-1 comprising amino acid residues 51-131 and residues 139-184, the latter of which codes for a zinc containing cysteine-rich domain. The cysteine-rich domain of Raf-1 is also reported to associate with other proteins, such as 14-3-3, and for selectively binding acidic phospholipids, particularly phosphatidylserine (PS). In the present study, we have investigated the consequences of progressive deletions and point mutations within the cysteine-rich domain of Raf-1 on its ability to bind PS. A reduced interaction with PS was observed in vitro for all deletion mutants of Raf-1 expressed either as full-length proteins or as fragments containing the isolated cysteine-rich domain. In particular, the cluster of basic amino acids R143, K144, and K148 appeared to be critical for interaction with PS, since substitution of all three residues to alanine resulted in a protein that failed to interact with liposomes enriched for PS. Expression of Raf-1 in vivo, containing point mutations in the cysteine-rich domain resulted in a truncated polypeptide that lacked both the Ras and PS binding sites and could no longer translocate to the plasma membrane upon serum stimulation. These results indicate that the basic residues 143, 144 and 148 in the anterior half of Raf-1 cysteine-rich domain play a role in the association with the lipid bilayer and possibly in protein stability, therefore they might contribute to Raf-1 localization and subsequent activation.
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