ArticleBiophysical journal2024
Positive feedback in Ras activation by full-length SOS arises from autoinhibition release mechanism.
Article in Biophysical journal, 2024. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 4 papers.
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4 citing papers in PubMed.
- LAT condensation gates PLCγ1 activation via bimodal LAT phosphorylation.Proceedings of the National Academy of Sciences of the United States of America · 2026Article
- Mesoscale simulations of membrane-tethered reactions to parameterize cell-scale models of signaling.Biophysical journal · 2026Article
- Mesoscale simulations of membrane-tethered reactions to parameterize cell-scale models of signaling.bioRxiv : the preprint server for biology · 2025Article
- Ras signaling mechanisms: New insights from single-molecule biophysics.Biophysical journal · 2024Article
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Abstract
Signaling through the Ras-MAPK pathway can exhibit switch-like activation, which has been attributed to the underlying positive feedback and bimodality in the activation of RasGDP to RasGTP by SOS. SOS contains both catalytic and allosteric Ras binding sites, and a common assumption is that allosteric activation selectively by RasGTP provides the mechanism of positive feedback. However, recent single-molecule studies have revealed that SOS catalytic rates are independent of the nucleotide state of Ras in the allosteric binding site, raising doubt about this as a positive feedback mechanism. Here, we perform detailed kinetic analyses of receptor-mediated recruitment of full-length SOS to the membrane while simultaneously monitoring its catalytic activation of Ras. These results, along with kinetic modeling, expose the autoinhibition release step in SOS, rather than either recruitment or allosteric activation, as the underlying mechanism giving rise to positive feedback in Ras activation.
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