ArticleProceedings of the National Academy of Sciences of the United States of America2020
Intrinsically disordered linkers control tethered kinases via effective concentration.
Article in Proceedings of the National Academy of Sciences of the United States of America, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 39 papers.
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Who cites it
39 citing papers in PubMed, 68 citations in OpenAlex.
- Effect of Linker Sequence on the Interdomain Dynamics of Self-Sufficient CYP116B5-SOX Chimeras.ACS omega · 2026Article
- AAK1-mediated phosphorylation of PDLIM5 and Talin1 promotes focal adhesion disassembly to accelerate cell migration.Nature communications · 2026Article
- Sequence- and Docking-Site-Dependent Contributions to Multi-Site Phosphorylation of an Intrinsically Disordered MAPK Substrate.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- 'Intelligent' proteins.Cellular and molecular life sciences : CMLS · 2025Review
- Noncovalent Lasso Entanglements are Common in Experimentally Derived Intrinsically Disordered Protein Ensembles and Strongly Influenced by Protein Length and Charge.The journal of physical chemistry. B · 2025Article
- Toward Design Principles for Biomolecular Condensates for Metabolic Pathways.Advanced biology · 2025Review
- Deciphering a profiling based on multiple post-translational modifications functionally associated regulatory patterns and therapeutic opportunities in human hepatocellular carcinoma.Molecular cancer · 2024Article
- Isoform-specific C-terminal phosphorylation drives autoinhibition of Casein kinase 1.Proceedings of the National Academy of Sciences of the United States of America · 2024Article
- The Disorderly Nature of Caliciviruses.Viruses · 2024Review
- Isoform-specific C-terminal phosphorylation drives autoinhibition of Casein Kinase 1.bioRxiv : the preprint server for biology · 2024Article
- Intact Transition Epitope Mapping-Force Interferences by Variable Extensions (ITEM-FIVE).Biomolecules · 2024Article
- The molecular basis for cellular function of intrinsically disordered protein regions.Nature reviews. Molecular cell biology · 2024Review
- An Autocatalytic Peptide Cyclase Improves Fidelity and Yield of Circular Peptides In Vivo and In Vitro.ACS synthetic biology · 2024Article
- Activation of caspase-9 on the apoptosome as studied by methyl-TROSY NMR.Proceedings of the National Academy of Sciences of the United States of America · 2023Article
- Intrinsically disordered regions are poised to act as sensors of cellular chemistry.Trends in biochemical sciences · 2023Review
- Phosphorylation-Assisted Luciferase Complementation Assay Designed to Monitor Kinase Activity and Kinase-Domain-Mediated Protein-Protein Binding.International journal of molecular sciences · 2023Article
- Architecture of the MKK6-p38α complex defines the basis of MAPK specificity and activation.Science (New York, N.Y.) · 2023Article
- Thumb-domain dynamics modulate the functional repertoire of DNA-Polymerase IV (DinB).Nucleic acids research · 2023Article
- Designer installation of a substrate recruitment domain to tailor enzyme specificity.Nature chemical biology · 2023Article
- Effects of Sequence Composition, Patterning and Hydrodynamics on the Conformation and Dynamics of Intrinsically Disordered Proteins.International journal of molecular sciences · 2023Article
Corrections and comments
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Authors and funding
2 authors at 1 institution in 1 country.
Funding
No grant is acknowledged in the PubMed record.
Abstract
Kinase specificity is crucial to the fidelity of signaling pathways, yet many pathways use the same kinases to achieve widely different effects. Specificity arises in part from the enzymatic domain but also from the physical tethering of kinases to their substrates. Such tethering can occur via protein interaction domains in the kinase or via anchoring and scaffolding proteins and can drastically increase the kinetics of phosphorylation. However, we do not know how such intracomplex reactions depend on the link between enzyme and substrate. Here we show that the kinetics of tethered kinases follow a Michaelis-Menten-like dependence on effective concentration. We find that phosphorylation kinetics scale with the length of the intrinsically disordered linkers that join the enzyme and substrate but that the scaling differs between substrates. Steady-state kinetics can only partially predict rates of tethered reactions as product release may obscure the rate of phosphotransfer. Our results suggest that changes in signaling complex architecture not only enhance the rates of phosphorylation reactions but may also alter the relative substrate usage. This suggests a mechanism for how scaffolding proteins can allosterically modify the output from a signaling pathway.
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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.