ArticleeLife2014
Ancestral resurrection reveals evolutionary mechanisms of kinase plasticity.
Article in eLife, 2014. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 34 papers.
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Who cites it
34 citing papers in PubMed.
- Evolutionary sequence and structural basis for the distinct conformational landscapes of Tyr and Ser/Thr kinases.Nature communications · 2024Article
- Ancestral Reconstruction and the Evolution of Protein Energy Landscapes.Annual review of biophysics · 2024Review
- Evolutionary sequence and structural basis for the distinct conformational landscapes of Tyr and Ser/Thr kinases.Research square · 2024Article
- Evolutionary sequence and structural basis for the distinct conformational landscapes of Tyr and Ser/Thr kinases.bioRxiv : the preprint server for biology · 2024Article
- Evolutionary Divergence of Phosphorylation to Regulate Interactive Protein Networks in Lower and Higher Species.International journal of molecular sciences · 2022Article
- Condensed-phase signaling can expand kinase specificity and respond to macromolecular crowding.Molecular cell · 2022Article
- Saturation mutagenesis of a predicted ancestral Syk-family kinase.Protein science : a publication of the Protein Society · 2022Article
- PCARE requires coiled coil, RP62 kinase-binding and EVH1 domain-binding motifs for ciliary expansion.Human molecular genetics · 2022Article
- Ancestral reconstruction of duplicated signaling proteins reveals the evolution of signaling specificity.eLife · 2022Article
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- Resurrection of ancestral effector caspases identifies novel networks for evolution of substrate specificity.The Biochemical journal · 2019Review
- Learning from ancestors.eLife · 2019Article
- Article
- Evolution of protein kinase substrate recognition at the active site.PLoS biology · 2019Article
- Comprehensive profiling of the STE20 kinase family defines features essential for selective substrate targeting and signaling output.PLoS biology · 2019Article
- Understanding molecular mechanisms in cell signaling through natural and artificial sequence variation.Nature structural & molecular biology · 2019Review
- Ancient mechanisms for the evolution of the bicoid homeodomain's function in fly development.eLife · 2018Article
- The burst-phase folding intermediate of ribonuclease H changes conformation over evolutionary history.Biopolymers · 2018Article
- Homing in: Mechanisms of Substrate Targeting by Protein Kinases.Trends in biochemical sciences · 2018Review
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Authors and funding
8 authors.
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Abstract
Protein kinases have evolved diverse specificities to enable cellular information processing. To gain insight into the mechanisms underlying kinase diversification, we studied the CMGC protein kinases using ancestral reconstruction. Within this group, the cyclin dependent kinases (CDKs) and mitogen activated protein kinases (MAPKs) require proline at the +1 position of their substrates, while Ime2 prefers arginine. The resurrected common ancestor of CDKs, MAPKs, and Ime2 could phosphorylate substrates with +1 proline or arginine, with preference for proline. This specificity changed to a strong preference for +1 arginine in the lineage leading to Ime2 via an intermediate with equal specificity for proline and arginine. Mutant analysis revealed that a variable residue within the kinase catalytic cleft, DFGx, modulates +1 specificity. Expansion of Ime2 kinase specificity by mutation of this residue did not cause dominant deleterious effects in vivo. Tolerance of cells to new specificities likely enabled the evolutionary divergence of kinases.
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