ReviewPhilosophical transactions of the Royal Society of London. Series B, Biological sciences2012
Design principles underpinning the regulatory diversity of protein kinases.
Review in Philosophical transactions of the Royal Society of London. Series B, Biological sciences, 2012. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 20 papers.
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Who cites it
20 citing papers in PubMed, 41 citations in OpenAlex.
- Sequence- and Docking-Site-Dependent Contributions to Multi-Site Phosphorylation of an Intrinsically Disordered MAPK Substrate.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2025Article
- Article
- Integration of a Randomized Sequence Scanning Approach in AlphaFold2 and Local Frustration Profiling of Conformational States Enable Interpretable Atomistic Characterization of Conformational Ensembles and Detection of Hidden Allosteric States in the ABL1 Protein Kinase.Journal of chemical theory and computation · 2024Article
- Tree visualizations of protein sequence embedding space enable improved functional clustering of diverse protein superfamilies.Briefings in bioinformatics · 2023Article
- Article
- Probing conformational landscapes and mechanisms of allosteric communication in the functional states of the ABL kinase domain using multiscale simulations and network-based mutational profiling of allosteric residue potentials.The Journal of chemical physics · 2022Article
- Granulovirus PK-1 kinase activity relies on a side-to-side dimerization mode centered on the regulatory αC helix.Nature communications · 2021Article
- Targeting Receptor Kinases in Colorectal Cancer.Cancers · 2019Review
- Acylated-acyl carrier protein stabilizes the Pseudomonas aeruginosa WaaP lipopolysaccharide heptose kinase.Scientific reports · 2018Article
- Optogenetically controlled protein kinases for regulation of cellular signaling.Chemical Society reviews · 2018Review
- Article
- Hydrophobic Core Variations Provide a Structural Framework for Tyrosine Kinase Evolution and Functional Specialization.PLoS genetics · 2016Article
- Identification and classification of small molecule kinases: insights into substrate recognition and specificity.BMC evolutionary biology · 2016Article
- Article
- Tighter αC-helix-αL16-helix interactions seem to make p38α less prone to activation by autophosphorylation than Hog1.Bioscience reports · 2016Article
- ProKinO: a unified resource for mining the cancer kinome.Human mutation · 2015Article
- Article
- Co-conserved MAPK features couple D-domain docking groove to distal allosteric sites via the C-terminal flanking tail.PloS one · 2015Article
- The p38β mitogen-activated protein kinase possesses an intrinsic autophosphorylation activity, generated by a short region composed of the α-G helix and MAPK insert.The Journal of biological chemistry · 2014Article
- Article
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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
Protein phosphorylation in eukaryotes is carried out by a large and diverse family of protein kinases, which display remarkable diversity and complexity in their modes of regulation. The complex modes of regulation have evolved as a consequence of natural selection operating on protein kinase sequences for billions of years. Here we describe how quantitative comparisons of protein kinase sequences from diverse organisms, in particular prokaryotes, have contributed to our understanding of the structural organization and evolution of allosteric regulation in the protein kinase domain. An emerging view from these studies is that regulatory diversity and complexity in the protein kinase domain evolved in a 'modular' fashion through elaboration of an ancient core component, which existed before the emergence of eukaryotes. The core component provided the conformational flexibility required for ATP binding and phosphoryl transfer in prokaryotic kinases, but evolved into a highly regulatable domain in eukaryotes through the addition of exaggerated structural features that facilitated tight allosteric control. Family and group-specific features are built upon the core component in eukaryotes to provide additional layers of control. We propose that 'modularity' and 'conformational flexibility' are key evolvable traits of the protein kinase domain that contributed to its extensive regulatory diversity and complexity.
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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.