Phosphotyrosine-mediated LAT assembly on membranes drives kinetic bifurcation in recruitment dynamics of the Ras activator SOS
Abstract
The assembly of cell surface receptors with downstream signaling molecules is a commonly occurring theme in multiple signaling systems. However, little is known about how these assemblies modulate reaction kinetics and the ultimate propagation of signals. Here, we reconstitute phosphotyrosine-mediated assembly of extended linker for the activation of T cells (LAT):growth factor receptor-bound protein 2 (Grb2):Son of Sevenless (SOS) networks, derived from the T-cell receptor signaling system, on supported membranes. Single-molecule dwell time distributions reveal two, well-differentiated kinetic species for both Grb2 and SOS on the LAT assemblies. The majority fraction of membrane-recruited Grb2 and SOS both exhibit fast kinetics and single exponential dwell time distributions, with average dwell times of hundreds of milliseconds. The minor fraction exhibits much slower kinetics, extending the dwell times to tens of seconds. Considering this result in the context of the multistep process by which the Ras GEF (guanine nucleotide exchange factor) activity of SOS is activated indicates that kinetic stabilization from the LAT assembly may be important. This kinetic proofreading effect would additionally serve as a stochastic noise filter by reducing the relative probability of spontaneous SOS activation in the absence of receptor triggering. In conclusion, the generality of receptor-mediated assembly suggests thatmore »
- Authors:
-
- Univ. of California, Berkeley, CA (United States). Dept. of Chemistry
- Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.; Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology
- Univ. of California, Berkeley, CA (United States). Dept. of Chemistry; Univ. of California, Berkeley, CA (United States). Howard Hughes Medical Inst.; Univ. of California, Berkeley, CA (United States). Dept. of Molecular and Cell Biology
- Publication Date:
- Research Org.:
- Lawrence Berkeley National Laboratory (LBNL), Berkeley, CA (United States)
- Sponsoring Org.:
- USDOE; National Institutes of Health (NIH)
- OSTI Identifier:
- 1379525
- Grant/Contract Number:
- AC02-05CH11231; P01 AI091580
- Resource Type:
- Accepted Manuscript
- Journal Name:
- Proceedings of the National Academy of Sciences of the United States of America
- Additional Journal Information:
- Journal Volume: 113; Journal Issue: 29; Journal ID: ISSN 0027-8424
- Publisher:
- National Academy of Sciences, Washington, DC (United States)
- Country of Publication:
- United States
- Language:
- English
- Subject:
- 60 APPLIED LIFE SCIENCES; 59 BASIC BIOLOGICAL SCIENCES; signal transduction; protein assembly; kinetic proofreading; membrane dwell time; single molecule
Citation Formats
Huang, William Y. C., Yan, Qingrong, Lin, Wan-Chen, Chung, Jean K., Hansen, Scott D., Christensen, Sune M., Tu, Hsiung-Lin, Kuriyan, John, and Groves, Jay T. Phosphotyrosine-mediated LAT assembly on membranes drives kinetic bifurcation in recruitment dynamics of the Ras activator SOS. United States: N. p., 2016.
Web. doi:10.1073/pnas.1602602113.
Huang, William Y. C., Yan, Qingrong, Lin, Wan-Chen, Chung, Jean K., Hansen, Scott D., Christensen, Sune M., Tu, Hsiung-Lin, Kuriyan, John, & Groves, Jay T. Phosphotyrosine-mediated LAT assembly on membranes drives kinetic bifurcation in recruitment dynamics of the Ras activator SOS. United States. https://doi.org/10.1073/pnas.1602602113
Huang, William Y. C., Yan, Qingrong, Lin, Wan-Chen, Chung, Jean K., Hansen, Scott D., Christensen, Sune M., Tu, Hsiung-Lin, Kuriyan, John, and Groves, Jay T. Fri .
"Phosphotyrosine-mediated LAT assembly on membranes drives kinetic bifurcation in recruitment dynamics of the Ras activator SOS". United States. https://doi.org/10.1073/pnas.1602602113. https://www.osti.gov/servlets/purl/1379525.
@article{osti_1379525,
title = {Phosphotyrosine-mediated LAT assembly on membranes drives kinetic bifurcation in recruitment dynamics of the Ras activator SOS},
author = {Huang, William Y. C. and Yan, Qingrong and Lin, Wan-Chen and Chung, Jean K. and Hansen, Scott D. and Christensen, Sune M. and Tu, Hsiung-Lin and Kuriyan, John and Groves, Jay T.},
abstractNote = {The assembly of cell surface receptors with downstream signaling molecules is a commonly occurring theme in multiple signaling systems. However, little is known about how these assemblies modulate reaction kinetics and the ultimate propagation of signals. Here, we reconstitute phosphotyrosine-mediated assembly of extended linker for the activation of T cells (LAT):growth factor receptor-bound protein 2 (Grb2):Son of Sevenless (SOS) networks, derived from the T-cell receptor signaling system, on supported membranes. Single-molecule dwell time distributions reveal two, well-differentiated kinetic species for both Grb2 and SOS on the LAT assemblies. The majority fraction of membrane-recruited Grb2 and SOS both exhibit fast kinetics and single exponential dwell time distributions, with average dwell times of hundreds of milliseconds. The minor fraction exhibits much slower kinetics, extending the dwell times to tens of seconds. Considering this result in the context of the multistep process by which the Ras GEF (guanine nucleotide exchange factor) activity of SOS is activated indicates that kinetic stabilization from the LAT assembly may be important. This kinetic proofreading effect would additionally serve as a stochastic noise filter by reducing the relative probability of spontaneous SOS activation in the absence of receptor triggering. In conclusion, the generality of receptor-mediated assembly suggests that such effects may play a role in multiple receptor proximal signaling processes.},
doi = {10.1073/pnas.1602602113},
journal = {Proceedings of the National Academy of Sciences of the United States of America},
number = 29,
volume = 113,
place = {United States},
year = {Fri Jul 01 00:00:00 EDT 2016},
month = {Fri Jul 01 00:00:00 EDT 2016}
}
Web of Science
Works referenced in this record:
Phase transitions in the assembly of multivalent signalling proteins
journal, March 2012
- Li, Pilong; Banjade, Sudeep; Cheng, Hui-Chun
- Nature, Vol. 483, Issue 7389
Eph Receptor Signaling and Ephrins
journal, September 2013
- Lisabeth, E. M.; Falivelli, G.; Pasquale, E. B.
- Cold Spring Harbor Perspectives in Biology, Vol. 5, Issue 9
The Grb2-mSos1 Complex Binds Phosphopeptides with Higher Affinity than Grb2
journal, November 1996
- Chook, Yuh Min; Gish, Gerald D.; Kay, Cyril M.
- Journal of Biological Chemistry, Vol. 271, Issue 48
Digital Signaling and Hysteresis Characterize Ras Activation in Lymphoid Cells
journal, January 2009
- Das, Jayajit; Ho, Mary; Zikherman, Julie
- Cell, Vol. 136, Issue 2
The role of T cell receptor signaling thresholds in guiding T cell fate decisions
journal, April 2015
- Zikherman, Julie; Au-Yeung, Byron
- Current Opinion in Immunology, Vol. 33
Monitoring the Waiting Time Sequence of Single Ras GTPase Activation Events Using Liposome Functionalized Zero-Mode Waveguides
journal, March 2016
- Christensen, Sune M.; Triplet, Meredith G.; Rhodes, Christopher
- Nano Letters, Vol. 16, Issue 4
Oligomerization of signaling complexes by the multipoint binding of GRB2 to both LAT and SOS1
journal, August 2006
- Houtman, Jon C. D.; Yamaguchi, Hiroshi; Barda-Saad, Mira
- Nature Structural & Molecular Biology, Vol. 13, Issue 9
Restriction of Receptor Movement Alters Cellular Response: Physical Force Sensing by EphA2
journal, March 2010
- Salaita, K.; Nair, P. M.; Petit, R. S.
- Science, Vol. 327, Issue 5971
Receptor Signaling Clusters in the Immune Synapse
journal, June 2012
- Dustin, Michael L.; Groves, Jay T.
- Annual Review of Biophysics, Vol. 41, Issue 1
Aggregation of Membrane Proteins by Cytosolic Cross-Linkers: Theory and Simulation of the LAT-Grb2-SOS1 System
journal, April 2009
- Nag, Ambarish; Monine, Michael I.; Faeder, James R.
- Biophysical Journal, Vol. 96, Issue 7
Single-Molecule Microscopy Reveals Plasma Membrane Microdomains Created by Protein-Protein Networks that Exclude or Trap Signaling Molecules in T Cells
journal, June 2005
- Douglass, Adam D.; Vale, Ronald D.
- Cell, Vol. 121, Issue 6
Membrane-dependent signal integration by the Ras activator Son of sevenless
journal, May 2008
- Gureasko, Jodi; Galush, William J.; Boykevisch, Sean
- Nature Structural & Molecular Biology, Vol. 15, Issue 5
TCR and Lat are expressed on separate protein islands on T cell membranes and concatenate during activation
journal, December 2009
- Lillemeier, Björn F.; Mörtelmaier, Manuel A.; Forstner, Martin B.
- Nature Immunology, Vol. 11, Issue 1
Fiji: an open-source platform for biological-image analysis
journal, June 2012
- Schindelin, Johannes; Arganda-Carreras, Ignacio; Frise, Erwin
- Nature Methods, Vol. 9, Issue 7
Binding Specificity of Multiprotein Signaling Complexes Is Determined by Both Cooperative Interactions and Affinity Preferences †
journal, April 2004
- Houtman, Jon C. D.; Higashimoto, Yuichiro; Dimasi, Nazzareno
- Biochemistry, Vol. 43, Issue 14
Kinetic Control of Histidine-Tagged Protein Surface Density on Supported Lipid Bilayers
journal, April 2008
- Nye, Jeffrey A.; Groves, Jay T.
- Langmuir, Vol. 24, Issue 8
Kinetic proofreading in T-cell receptor signal transduction.
journal, May 1995
- McKeithan, T. W.
- Proceedings of the National Academy of Sciences, Vol. 92, Issue 11
Cell Signaling by Receptor Tyrosine Kinases
journal, October 2000
- Schlessinger, Joseph
- Cell, Vol. 103, Issue 2
Spatial Organization of EphA2 at the Cell-Cell Interface Modulates Trans-Endocytosis of EphrinA1
journal, May 2014
- Greene, Adrienne C.; Lord, Samuel J.; Tian, Aiwei
- Biophysical Journal, Vol. 106, Issue 10
The Ability of Sos1 to Oligomerize the Adaptor Protein LAT Is Separable from Its Guanine Nucleotide Exchange Activity in Vivo
journal, November 2013
- Kortum, R. L.; Balagopalan, L.; Alexander, C. P.
- Science Signaling, Vol. 6, Issue 301
Identification of the Minimal Tyrosine Residues Required for Linker for Activation of T Cell Function
journal, June 2001
- Lin, Joseph; Weiss, Arthur
- Journal of Biological Chemistry, Vol. 276, Issue 31
Methods in Statistical Kinetics
book, January 2010
- Moffitt, Jeffrey R.; Chemla, Yann R.; Bustamante, Carlos
- Methods in Enzymology
Ras activation by SOS: Allosteric regulation by altered fluctuation dynamics
journal, July 2014
- Iversen, Lars; Tu, Hsiung-Lin; Lin, Wan-Chen
- Science, Vol. 345, Issue 6192
Mapping the Zap-70 phosphorylation sites on LAT (linker for activation of T cells) required for recruitment and activation of signalling proteins in T cells
journal, May 2001
- Paz, Pedro E.; Wang, Soujuan; Clarke, Holly
- Biochemical Journal, Vol. 356, Issue 2
Bayesian Detection of Intensity Changes in Single Molecule and Molecular Dynamics Trajectories
journal, January 2010
- Ensign, Daniel L.; Pande, Vijay S.
- The Journal of Physical Chemistry B, Vol. 114, Issue 1
H-Ras forms dimers on membrane surfaces via a protein-protein interface
journal, February 2014
- Lin, W. -C.; Iversen, L.; Tu, H. -L.
- Proceedings of the National Academy of Sciences, Vol. 111, Issue 8
Dynamic multiple-target tracing to probe spatiotemporal cartography of cell membranes
journal, July 2008
- Sergé, Arnauld; Bertaux, Nicolas; Rigneault, Hervé
- Nature Methods, Vol. 5, Issue 8
Molecular mechanisms in signal transduction at the membrane
journal, May 2010
- Groves, Jay T.; Kuriyan, John
- Nature Structural & Molecular Biology, Vol. 17, Issue 6
Cell Signaling in Space and Time: Where Proteins Come Together and When They’re Apart
journal, November 2009
- Scott, John D.; Pawson, Tony
- Science, Vol. 326, Issue 5957
Size-Based Chromatography of Signaling Clusters in a Living Cell Membrane
journal, April 2014
- Caculitan, Niña G.; Kai, Hiroyuki; Liu, Eulanca Y.
- Nano Letters, Vol. 14, Issue 5
Fast rebinding increases dwell time of Src homology 2 (SH2)-containing proteins near the plasma membrane
journal, August 2012
- Oh, D.; Ogiue-Ikeda, M.; Jadwin, J. A.
- Proceedings of the National Academy of Sciences, Vol. 109, Issue 35
Kinetic Proofreading: A New Mechanism for Reducing Errors in Biosynthetic Processes Requiring High Specificity
journal, October 1974
- Hopfield, J. J.
- Proceedings of the National Academy of Sciences, Vol. 71, Issue 10
Minimal Requirement of Tyrosine Residues of Linker for Activation of T Cells in TCR Signaling and Thymocyte Development
journal, January 2003
- Zhu, Minghua; Janssen, Erin; Zhang, Weiguo
- The Journal of Immunology, Vol. 170, Issue 1
On the Mechanism of Trolox as Antiblinking and Antibleaching Reagent
journal, April 2009
- Cordes, Thorben; Vogelsang, Jan; Tinnefeld, Philip
- Journal of the American Chemical Society, Vol. 131, Issue 14
Nanoscale Obstacle Arrays Frustrate Transport of EphA2–Ephrin-A1 Clusters in Cancer Cell Lines
journal, June 2013
- Lohmüller, Theobald; Xu, Qian; Groves, Jay T.
- Nano Letters, Vol. 13, Issue 7
Photobleaching kinetics of fluorescein in quantitative fluorescence microscopy
journal, June 1995
- Song, L.; Hennink, E. J.; Young, I. T.
- Biophysical Journal, Vol. 68, Issue 6
Single-Molecule Michaelis−Menten Equations
journal, October 2005
- Kou, S. C.; Cherayil, Binny J.; Min, Wei
- The Journal of Physical Chemistry B, Vol. 109, Issue 41
Concepts and consequences of Eph receptor clustering
journal, February 2012
- Janes, Peter W.; Nievergall, Eva; Lackmann, Martin
- Seminars in Cell & Developmental Biology, Vol. 23, Issue 1
Role of the histone domain in the autoinhibition and activation of the Ras activator Son of Sevenless
journal, February 2010
- Gureasko, Jodi; Kuchment, Olga; Makino, Debora Lika
- Proceedings of the National Academy of Sciences, Vol. 107, Issue 8
The Grb2-mSos1 complex binds phosphopeptides with higher affinity than Grb2.
journal, February 1997
- Chook, Yuh Min; Gish, Gerald D.; Kay, Cyril M.
- Journal of Biological Chemistry, Vol. 272, Issue 6
Voltage-gated ion channels
book, January 2011
- Keynes, Richard D.; Aidley, David J.; Huang, Christopher L. -H.
- Nerve and Muscle
Works referencing / citing this record:
Multicomponent Supported Membrane Microarray for Monitoring Spatially Resolved Cellular Signaling Reactions
journal, February 2018
- Biswas, Kabir H.; Zhongwen, Chen; Dubey, Alok Kumar
- Advanced Biosystems, Vol. 2, Issue 4
Integrin and cadherin clusters: A robust way to organize adhesions for cell mechanics
journal, December 2016
- Changede, Rishita; Sheetz, Michael
- BioEssays, Vol. 39, Issue 1
Regulatory mechanisms in T cell receptor signalling
journal, May 2018
- Gaud, Guillaume; Lesourne, Renaud; Love, Paul E.
- Nature Reviews Immunology, Vol. 18, Issue 8
Understanding T cell signaling using membrane reconstitution
journal, August 2019
- Hui, Enfu
- Immunological Reviews, Vol. 291, Issue 1
A molecular assembly phase transition and kinetic proofreading modulate Ras activation by SOS
journal, March 2019
- Huang, William Y. C.; Alvarez, Steven; Kondo, Yasushi
- Science, Vol. 363, Issue 6431
Stoichiometry controls activity of phase-separated clusters of actin signaling proteins
journal, March 2019
- Case, Lindsay B.; Zhang, Xu; Ditlev, Jonathon A.
- Science, Vol. 363, Issue 6431
Mapping the stochastic sequence of individual ligand-receptor binding events to cellular activation: T cells act on the rare events
journal, January 2019
- Lin, Jenny J. Y.; Low-Nam, Shalini T.; Alfieri, Katherine N.
- Science Signaling, Vol. 12, Issue 564
More from less – bottom-up reconstitution of cell biology
journal, February 2019
- Ganzinger, Kristina A.; Schwille, Petra
- Journal of Cell Science, Vol. 132, Issue 4
Light-based tuning of ligand half-life supports kinetic proofreading model of T cell signaling
journal, April 2019
- Tischer, Doug K.; Weiner, Orion David
- eLife, Vol. 8
Kinetics of cytokine receptor trafficking determine signaling and functional selectivity
journal, November 2019
- Martinez-Fabregas, Jonathan; Wilmes, Stephan; Wang, Luopin
- eLife, Vol. 8
Multiple sources of signal amplification within the B cell Ras/MAPK pathway
journal, September 2018
- McLaurin, Justin D.; Weiner, Orion D.
- Molecular Biology of the Cell
Kinetics of cytokine receptor trafficking determine signaling and functional selectivity
journal, November 2019
- Martinez-Fabregas, Jonathan; Wilmes, Stephan; Wang, Luopin
- eLife, Vol. 8