Early emergence of negative regulation of the tyrosine kinase Src by the C-terminal Src kinase
| Autor: | Douglas M. Fowler, Barbara Taskinen, Evandro Ferrada |
|---|---|
| Rok vydání: | 2017 |
| Předmět: |
0301 basic medicine
Aquatic Organisms Protozoan Proteins Mitogen-activated protein kinase kinase Biochemistry Receptor tyrosine kinase Substrate Specificity MAP2K7 CSK Tyrosine-Protein Kinase 03 medical and health sciences Species Specificity Two-Hybrid System Techniques Protein Interaction Domains and Motifs Amino Acid Sequence Molecular Biology Choanoflagellata Conserved Sequence Phylogeny Tyrosine-protein kinase CSK Sequence Homology Amino Acid MAP kinase kinase kinase biology Computational Biology Cell Biology Recombinant Proteins Cell biology Kinetics src-Family Kinases 030104 developmental biology Amino Acid Substitution Structural Homology Protein Mutation biology.protein Cyclin-dependent kinase 9 Sequence Alignment Tyrosine kinase Signal Transduction Proto-oncogene tyrosine-protein kinase Src |
| Zdroj: | Journal of Biological Chemistry. 292:18518-18529 |
| ISSN: | 0021-9258 |
| DOI: | 10.1074/jbc.m117.811174 |
| Popis: | Stringent regulation of tyrosine kinase activity is essential for normal cellular function. In humans, the tyrosine kinase Src is inhibited via phosphorylation of its C-terminal tail by another kinase, C-terminal Src kinase (Csk). Although Src and Csk orthologs are present across holozoan organisms, including animals and protists, the Csk–Src negative regulatory mechanism appears to have evolved gradually. For example, in choanoflagellates, Src and Csk are both active, but the negative regulatory mechanism is reportedly absent. In filastereans, a protist clade closely related to choanoflagellates, Src is active, but Csk is apparently inactive. In this study, we use a combination of bioinformatics, in vitro kinase assays, and yeast-based growth assays to characterize holozoan Src and Csk orthologs. We show that, despite appreciable differences in domain architecture, Csk from Corallochytrium limacisporum, a highly diverged holozoan marine protist, is active and can inhibit Src. However, in comparison with other Csk orthologs, Corallochytrium Csk displays broad substrate specificity and inhibits Src in an activity-independent manner. Furthermore, in contrast to previous studies, we show that Csk from the filasterean Capsaspora owczarzaki is active and that the Csk–Src negative regulatory mechanism is present in Csk and Src proteins from C. owczarzaki and the choanoflagellate Monosiga brevicollis. Our results suggest that negative regulation of Src by Csk is more ancient than previously thought and that it might be conserved across all holozoan species. |
| Databáze: | OpenAIRE |
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