Cited by 155Protein Kinase Regulation and GTPase SignalingCellular transport and secretionAdvanced Fluorescence Microscopy Techniques

Ras activation by SOS: Allosteric regulation by altered fluctuation dynamics

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Iversen, Lars, Tu, Hsiung-Lin, Lin, Wan-Chen, Christensen, Sune M., Abel, Steven M., Iwig, Jeff, Wu, Hung-Jen, Gureasko, Jodi +9 more·2014·Science

Abstract

Outliers dominate signaling at cell membrane: SOS enzymes act at cell membranes to activate Ras, a regulatory protein often overactive in cancer cells. Iversen et al. devised a system where they could observe the activity of individual enzymes at work. The single SOS molecules occupied stable states that varied greatly in their catalytic activity. Regulation appeared to occur by altering the time spent in active states. The overall activity of SOS was determined by just a few molecules that achieved the highest catalytic activity. The methods described should allow further detailed kinetic analysis of this and other signaling events that occur at the cell membrane — properties that it is not possible to discern from bulk biochemical measurements. Science , this issue p. 50

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Authors
Iversen, L., Tu, H.-L., Lin, W.-C., Christensen, S. M., Abel, S. M., Iwig, J., Wu, H.-J., Gureasko, J., Rhodes, C., Petit, R. S., Hansen, S. D., Thill, P., Yu, C.-H., Stamou, D., Chakraborty, A. K., Kuriyan, J., & Groves, J. T.
Affiliations
  • Howard Hughes Medical Institute (US)
  • Massachusetts Institute of Technology (US)
  • University of California, Berkeley (US)
  • National University of Singapore (SG)
  • University of Copenhagen (DK)
  • Ragon Institute of MGH, MIT and Harvard (US)
Corresponding author
  • Iversen, Lars
  • Tu, Hsiung-Lin
  • Groves, Jay T.
Venue
Science
Published
2014-07-04
Volume
345
Issue
6192
Pages
50-54
ISSN
  • 0036-8075 (ISSN-L)
  • 1095-9203
OpenAlex
W2043601243
Cited by
154
References
68
Citations by year
2026: 12 · 2025: 12 · 2024: 11 · 2023: 12 · 2022: 11 · 2021: 15 · 2020: 4 · 2019: 15 · 2018: 15 · 2017: 5 · 2016: 27 · 2015: 10 · 2014: 5
FWCI
6.39
Type
journal article
Language
en
Open access
Locations
  • Science (publishedVersion)
  • PubMed (publishedVersion)
  • PubMed Central (acceptedVersion)
  • eScholarship (California Digital Library) (submittedVersion)
  • The HKU Scholars Hub (University of Hong Kong) (submittedVersion)
  • Research at the University of Copenhagen (University of Copenhagen) (submittedVersion)
Funders
  • Howard Hughes Medical Institute
  • National University of Singapore
  • Danmarks Frie Forskningsfond
  • Mechanobiology Institute, Singapore
  • National Institutes of Health
  • National Institute of Allergy and Infectious Diseases (P01AI091580)
Topics
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Molecular Biology › Protein Kinase Regulation and GTPase Signaling
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Cell Biology › Cellular transport and secretion
  • Life Sciences › Biochemistry, Genetics and Molecular Biology › Biophysics › Advanced Fluorescence Microscopy Techniques
Keywords
H-Ras, Son of Sevenless, SO, small GTPase activation, allosteric regulation, nucleotide exchange, single-molecule kinetics, stochastic fluctuations, Ras-GTP, signal transduction, enzyme turnover rate
MeSH terms
Allosteric Regulation, Enzyme Activation, Humans, Kinetics, Nucleotides, Proto-Oncogene Proteins p21(ras), Crystallography, X-Ray, Catalytic Domain, Son of Sevenless Protein, Drosophila, Protein Interaction Domains and Motifs

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