ArticleScience advances2017
Biophysical assay for tethered signaling reactions reveals tether-controlled activity for the phosphatase SHP-1.
Article in Science advances, 2017. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed.
- A Multiscale Signaling-Biophysical Framework Reveals Mechanisms of Macrophage-Mediated RBC Clearance in Sickle Cell and Gaucher Disease.bioRxiv : the preprint server for biology · 2026Article
- The molecular reach of antibodies crucially underpins their viral neutralisation capacity.Nature communications · 2025Article
- Competition between physical search and a weak-to-strong transition rate-limits kinesin binding times.PLoS computational biology · 2024Article
- ADP release can explain spatially-dependent kinesin binding times.bioRxiv : the preprint server for biology · 2023Article
- The optimal docking strength for reversibly tethered kinases.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Spatially resolved in silico modeling of NKG2D signaling kinetics suggests a key role of NKG2D and Vav1 Co-clustering in generating natural killer cell activation.PLoS computational biology · 2022Article
- Dephosphorylation accelerates the dissociation of ZAP70 from the T cell receptor.Proceedings of the National Academy of Sciences of the United States of America · 2022Article
- Molecular features underlying differential SHP1/SHP2 binding of immune checkpoint receptors.eLife · 2021Article
- Determination of the molecular reach of the protein tyrosine phosphatase SHP-1.Biophysical journal · 2021Article
- Intrinsic Disorder in the T Cell Receptor Creates Cooperativity and Controls ZAP70 Binding.Biophysical journal · 2021Article
- PD-1 and BTLA regulate T cell signaling differentially and only partially through SHP1 and SHP2.The Journal of cell biology · 2020Article
- The Influence of Molecular Reach and Diffusivity on the Efficacy of Membrane-Confined Reactions.Biophysical journal · 2019Article
- Receptor-Ligand Rebinding Kinetics in Confinement.Biophysical journal · 2019Article
- Understanding the Dynamics of T-Cell Activation in Health and Disease Through the Lens of Computational Modeling.JCO clinical cancer informatics · 2019Review
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7 authors.
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Abstract
Tethered enzymatic reactions are ubiquitous in signaling networks but are poorly understood. A previously unreported mathematical analysis is established for tethered signaling reactions in surface plasmon resonance (SPR). Applying the method to the phosphatase SHP-1 interacting with a phosphorylated tether corresponding to an immune receptor cytoplasmic tail provides five biophysical/biochemical constants from a single SPR experiment: two binding rates, two catalytic rates, and a reach parameter. Tether binding increases the activity of SHP-1 by 900-fold through a binding-induced allosteric activation (20-fold) and a more significant increase in local substrate concentration (45-fold). The reach parameter indicates that this local substrate concentration is exquisitely sensitive to receptor clustering. We further show that truncation of the tether leads not only to a lower reach but also to lower binding and catalysis. This work establishes a new framework for studying tethered signaling processes and highlights the tether as a control parameter in clustered receptor signaling.
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