ArticleBiophysical journal2011
Ultrasensitivity in multisite phosphorylation of membrane-anchored proteins.
Article in Biophysical journal, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 31 papers.
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Trials whose registry record cites this paper, or whose number appears in the abstract. A trial that started after this paper was published is citing it as background, not reporting it.
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Who cites it
31 citing papers in PubMed, 51 citations in OpenAlex.
- Kinetics of diffusion-influenced multisite phosphorylation with enzyme reactivation.Biopolymers · 2024Article
- 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
- Multisite reversible association in membranes and solutions: From non-Markovian to Markovian kinetics.The Journal of chemical physics · 2020Article
- The Beacon Calculus: A formal method for the flexible and concise modelling of biological systems.PLoS computational biology · 2020Article
- The Influence of Molecular Reach and Diffusivity on the Efficacy of Membrane-Confined Reactions.Biophysical journal · 2019Article
- Receptor recharge time drastically reduces the number of captured particles.PLoS computational biology · 2018Article
- β-adrenergic signaling broadly contributes to LTP induction.PLoS computational biology · 2017Article
- Including Rebinding Reactions in Well-Mixed Models of Distributive Biochemical Reactions.Biophysical journal · 2016Article
- Multisite Phosphorylation Modulates the T Cell Receptor ζ-Chain Potency but not the Switchlike Response.Biophysical journal · 2016Article
- Reductionism Is Dead: Long Live Reductionism! Systems Modeling Needs Reductionist Experiments.Biophysical journal · 2016Article
- Control of βAR- and N-methyl-D-aspartate (NMDA) Receptor-Dependent cAMP Dynamics in Hippocampal Neurons.PLoS computational biology · 2016Article
- Influence of diffusion on the kinetics of multisite phosphorylation.Protein science : a publication of the Protein Society · 2016Article
- The robustness of proofreading to crowding-induced pseudo-processivity in the MAPK pathway.Biophysical journal · 2014Article
- Biosensor architectures for high-fidelity reporting of cellular signaling.Biophysical journal · 2014Article
- Physicochemical properties of cells and their effects on intrinsically disordered proteins (IDPs).Chemical reviews · 2014Review
- Enhancement of tunability of MAPK cascade due to coexistence of processive and distributive phosphorylation mechanisms.Biophysical journal · 2014Article
- In vitro membrane reconstitution of the T-cell receptor proximal signaling network.Nature structural & molecular biology · 2014Article
- Article
- Diffusion modifies the connectivity of kinetic schemes for multisite binding and catalysis.Proceedings of the National Academy of Sciences of the United States of America · 2013Article
- Stochastic transitions in a bistable reaction system on the membrane.Journal of the Royal Society, Interface · 2013Article
Corrections and comments
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Authors and funding
3 authors at 2 institutions in 1 country.
Funding
Abstract
Cellular signaling is initially confined to the plasma membrane, where the cytoplasmic tails of surface receptors and other membrane-anchored proteins are phosphorylated in response to ligand binding. These proteins often contain multiple phosphorylation sites that are regulated by membrane-confined enzymes. Phosphorylation of these proteins is thought to be tightly regulated, because they initiate and regulate signaling cascades leading to cellular activation, yet how their phosphorylation is regulated is poorly understood. Ultrasensitive or switchlike responses in their phosphorylation state are not expected because the modifying enzymes are in excess. Here, we describe a novel mechanism of ultrasensitivity exhibited by multisite membrane-anchored proteins, but not cytosolic proteins, even when enzymes are in excess. The mechanism underlying this concentration-independent ultrasensitivity is the local saturation of a single enzyme by multiple sites on the substrate. Local saturation is a passive process arising from slow membrane diffusion, steric hindrances, and multiple sites, and therefore may be widely applicable. Critical to this ultrasensitivity is the brief enzymatic inactivation that follows substrate modification. Computations are presented using ordinary differential equations and stochastic spatial simulations. We propose a new role, to our knowledge, for multisite membrane-anchored proteins, discuss experiments that can be used to probe the model, and relate our findings to previous theoretical work.
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Registered trials
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.