ArticleBiophysical journal2014
The robustness of proofreading to crowding-induced pseudo-processivity in the MAPK pathway.
Article in Biophysical journal, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 6 papers.
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Who cites it
6 citing papers in PubMed.
- Investigating molecular crowding during cell division and hyperosmotic stress in budding yeast with FRET.Current topics in membranes · 2021Article
- Liquid-Liquid Phase Separation in Crowded Environments.International journal of molecular sciences · 2020Review
- Protein Clusters in Phosphotyrosine Signal Transduction.Journal of molecular biology · 2018Review
- Including Rebinding Reactions in Well-Mixed Models of Distributive Biochemical Reactions.Biophysical journal · 2016Article
- Intrinsic limits to gene regulation by global crosstalk.Nature communications · 2016Article
- Influence of diffusion on the kinetics of multisite phosphorylation.Protein science : a publication of the Protein Society · 2016Article
Corrections and comments
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Authors and funding
2 authors.
Funding
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Abstract
Double phosphorylation of protein kinases is a common feature of signaling cascades. This motif may reduce cross-talk between signaling pathways because the second phosphorylation site allows for proofreading, especially when phosphorylation is distributive rather than processive. Recent studies suggest that phosphorylation can be pseudo-processive in the crowded cellular environment, since rebinding after the first phosphorylation is enhanced by slow diffusion. Here, we use a simple model with unsaturated reactants to show that specificity for one substrate over another drops as rebinding increases and pseudo-processive behavior becomes possible. However, this loss of specificity with increased rebinding is typically also observed if two distinct enzyme species are required for phosphorylation, i.e., when the system is necessarily distributive. Thus the loss of specificity is due to an intrinsic reduction in selectivity with increased rebinding, which benefits inefficient reactions, rather than pseudo-processivity itself. We also show that proofreading can remain effective when the intended signaling pathway exhibits high levels of rebinding-induced pseudo-processivity, unlike other proposed advantages of the dual phosphorylation motif.
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