Ancestral resurrection reveals evolutionary mechanisms of kinase plasticity
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...
| Main Authors: | , , , , , , , |
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| Format: | Article |
| Language: | English |
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eLife Sciences Publications Ltd
2014-10-01
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| Series: | eLife |
| Subjects: | |
| Online Access: | https://elifesciences.org/articles/04126 |
| _version_ | 1818028355630399488 |
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| author | Conor J Howard Victor Hanson-Smith Kristopher J Kennedy Chad J Miller Hua Jane Lou Alexander D Johnson Benjamin E Turk Liam J Holt |
| author_facet | Conor J Howard Victor Hanson-Smith Kristopher J Kennedy Chad J Miller Hua Jane Lou Alexander D Johnson Benjamin E Turk Liam J Holt |
| author_sort | Conor J Howard |
| collection | DOAJ |
| description | 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. |
| first_indexed | 2024-12-10T05:02:29Z |
| format | Article |
| id | doaj.art-efd49d302c32441494c383b83fc91f84 |
| institution | Directory Open Access Journal |
| issn | 2050-084X |
| language | English |
| last_indexed | 2024-12-10T05:02:29Z |
| publishDate | 2014-10-01 |
| publisher | eLife Sciences Publications Ltd |
| record_format | Article |
| series | eLife |
| spelling | doaj.art-efd49d302c32441494c383b83fc91f842022-12-22T02:01:22ZengeLife Sciences Publications LtdeLife2050-084X2014-10-01310.7554/eLife.04126Ancestral resurrection reveals evolutionary mechanisms of kinase plasticityConor J Howard0Victor Hanson-Smith1Kristopher J Kennedy2Chad J Miller3Hua Jane Lou4Alexander D Johnson5Benjamin E Turk6Liam J Holt7https://orcid.org/0000-0002-4002-0861Department of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, United StatesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesDepartment of Pharmacology, Yale University School of Medicine, New Haven, United StatesDepartment of Pharmacology, Yale University School of Medicine, New Haven, United StatesDepartment of Microbiology and Immunology, University of California, San Francisco, San Francisco, United StatesDepartment of Pharmacology, Yale University School of Medicine, New Haven, United StatesDepartment of Molecular and Cell Biology, University of California, Berkeley, Berkeley, United StatesProtein 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.https://elifesciences.org/articles/04126protein kinaseevolutionancestral reconstructioncyclin-dependent kinaseIme2phosphoregulatory network |
| spellingShingle | Conor J Howard Victor Hanson-Smith Kristopher J Kennedy Chad J Miller Hua Jane Lou Alexander D Johnson Benjamin E Turk Liam J Holt Ancestral resurrection reveals evolutionary mechanisms of kinase plasticity eLife protein kinase evolution ancestral reconstruction cyclin-dependent kinase Ime2 phosphoregulatory network |
| title | Ancestral resurrection reveals evolutionary mechanisms of kinase plasticity |
| title_full | Ancestral resurrection reveals evolutionary mechanisms of kinase plasticity |
| title_fullStr | Ancestral resurrection reveals evolutionary mechanisms of kinase plasticity |
| title_full_unstemmed | Ancestral resurrection reveals evolutionary mechanisms of kinase plasticity |
| title_short | Ancestral resurrection reveals evolutionary mechanisms of kinase plasticity |
| title_sort | ancestral resurrection reveals evolutionary mechanisms of kinase plasticity |
| topic | protein kinase evolution ancestral reconstruction cyclin-dependent kinase Ime2 phosphoregulatory network |
| url | https://elifesciences.org/articles/04126 |
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