ArticleBiophysical journal2009
A RasGTP-induced conformational change in C-RAF is essential for accurate molecular recognition.
Article in Biophysical journal, 2009. 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, 36 citations in OpenAlex.
- Regulation of RAF family kinases: new insights from recent structural and biochemical studies.Biochemical Society transactions · 2024Review
- Multiplexed imaging for probing RAS-RAF interactions in living cells.Biochimica et biophysica acta. Biomembranes · 2023Article
- Review
- Single-Molecular Förster Resonance Energy Transfer Measurement on Structures and Interactions of Biomolecules.Micromachines · 2021Review
- Multiple sources of signal amplification within the B-cell Ras/MAPK pathway.Molecular biology of the cell · 2019Article
- Ras-Mediated Activation of the Raf Family Kinases.Cold Spring Harbor perspectives in medicine · 2019Review
- The dimer-dependent catalytic activity of RAF family kinases is revealed through characterizing their oncogenic mutants.Oncogene · 2018Article
- Single-molecule fluorescence-based analysis of protein conformation, interaction, and oligomerization in cellular systems.Biophysical reviews · 2018Review
- Mutation-Specific Mechanisms of Hyperactivation of Noonan Syndrome SOS Molecules Detected with Single-molecule Imaging in Living Cells.Scientific reports · 2017Article
- Coupled excitable Ras and F-actin activation mediates spontaneous pseudopod formation and directed cell movement.Molecular biology of the cell · 2017Article
- Single-molecule fluorescence imaging of RalGDS on cell surfaces during signal transduction from Ras to Ral.Biophysics and physicobiology · 2017Article
- Modeling Cellular Noise Underlying Heterogeneous Cell Responses in the Epidermal Growth Factor Signaling Pathway.PLoS computational biology · 2016Article
- The significance of membrane fluidity of feeder cell-derived substrates for maintenance of iPS cell stemness.Scientific reports · 2015Article
- Variational Bayes analysis of a photon-based hidden Markov model for single-molecule FRET trajectories.Biophysical journal · 2012Article
- Dynamics of Ras complexes observed in living cells.Sensors (Basel, Switzerland) · 2012Article
- Activation kinetics of RAF protein in the ternary complex of RAF, RAS-GTP, and kinase on the plasma membrane of living cells: single-molecule imaging analysis.The Journal of biological chemistry · 2011Article
- Mechanistic principles of RAF kinase signaling.Cellular and molecular life sciences : CMLS · 2011Review
- Live-cell microscopy reveals small molecule inhibitor effects on MAPK pathway dynamics.PloS one · 2011Article
Corrections and comments
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Authors and funding
4 authors at 3 institutions in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
The dysregulation of Ras-RAF signaling is associated with many types of human cancer. However, the kinetic and dynamic features of the mutual molecular recognition of Ras and RAF remain unknown. Here, we developed a technique for imaging single-pair fluorescence resonance energy transfer in living cells, and coupled this technique to single-molecule kinetic analysis to investigate how C-RAF (a subtype of RAF) molecules distinguish the active form of Ras (RasGTP) from the inactive form (RasGDP). Functional fragments of C-RAF containing the Ras-binding domains did not detect the switch in Ras activity in living cells as efficiently as did C-RAF. Single-molecule analysis showed that RasGDP associates with closed-conformation C-RAF, whereas the association of C-RAF with RasGTP immediately triggers the open RAF conformation, which induces an effective interaction between C-RAF and RasGTP. Spontaneous conformational changes from closed C-RAF to the open form rarely occur in quiescent cells. The conformational change in C-RAF is so important to Ras-RAF molecular recognition that C-RAF mutants lacking the conformational change cannot distinguish between RasGDP and RasGTP. The manipulation of the conformation of an effector molecule is a newly identified function of RasGTP.
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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.