Biomaterial Database

Early emergence of negative regulation of the tyrosine kinase Src by the C-terminal Src kinase. 2017

Barbara Taskinen, and Evandro Ferrada, and Douglas M Fowler

From the Department of Genome Sciences, University of Washington, Seattle, Washington 98195-5065 and.

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.

UI	MeSH Term	Description	Entries
D007700	Kinetics	The rate dynamics in chemical or physical systems.
D009154	Mutation	Any detectable and heritable change in the genetic material that causes a change in the GENOTYPE and which is transmitted to daughter cells and to succeeding generations.	Mutations
D010802	Phylogeny	The relationships of groups of organisms as reflected by their genetic makeup.	Community Phylogenetics,Molecular Phylogenetics,Phylogenetic Analyses,Phylogenetic Analysis,Phylogenetic Clustering,Phylogenetic Comparative Analysis,Phylogenetic Comparative Methods,Phylogenetic Distance,Phylogenetic Generalized Least Squares,Phylogenetic Groups,Phylogenetic Incongruence,Phylogenetic Inference,Phylogenetic Networks,Phylogenetic Reconstruction,Phylogenetic Relatedness,Phylogenetic Relationships,Phylogenetic Signal,Phylogenetic Structure,Phylogenetic Tree,Phylogenetic Trees,Phylogenomics,Analyse, Phylogenetic,Analysis, Phylogenetic,Analysis, Phylogenetic Comparative,Clustering, Phylogenetic,Community Phylogenetic,Comparative Analysis, Phylogenetic,Comparative Method, Phylogenetic,Distance, Phylogenetic,Group, Phylogenetic,Incongruence, Phylogenetic,Inference, Phylogenetic,Method, Phylogenetic Comparative,Molecular Phylogenetic,Network, Phylogenetic,Phylogenetic Analyse,Phylogenetic Clusterings,Phylogenetic Comparative Analyses,Phylogenetic Comparative Method,Phylogenetic Distances,Phylogenetic Group,Phylogenetic Incongruences,Phylogenetic Inferences,Phylogenetic Network,Phylogenetic Reconstructions,Phylogenetic Relatednesses,Phylogenetic Relationship,Phylogenetic Signals,Phylogenetic Structures,Phylogenetic, Community,Phylogenetic, Molecular,Phylogenies,Phylogenomic,Reconstruction, Phylogenetic,Relatedness, Phylogenetic,Relationship, Phylogenetic,Signal, Phylogenetic,Structure, Phylogenetic,Tree, Phylogenetic
D011994	Recombinant Proteins	Proteins prepared by recombinant DNA technology.	Biosynthetic Protein,Biosynthetic Proteins,DNA Recombinant Proteins,Recombinant Protein,Proteins, Biosynthetic,Proteins, Recombinant DNA,DNA Proteins, Recombinant,Protein, Biosynthetic,Protein, Recombinant,Proteins, DNA Recombinant,Proteins, Recombinant,Recombinant DNA Proteins,Recombinant Proteins, DNA
D000081247	CSK Tyrosine-Protein Kinase	Protein tyrosine kinases that phosphorylate tyrosine residues located in the C-terminal tails of SRC-FAMILY KINASES.	C-Terminal Src Kinase,Carboxy-Terminal Src Kinase,Protein Tyrosine Kinase p50(csk),Protein-Tyrosine Kinase C-Terminal Src Kinase,Protein-Tyrosine Kinase c-src,Tyrosine Protein Kinase p50csk,Tyrosine-Protein Kinase CSK,c-src Kinase,c-src Tyrosine Kinase,CSK-src,p50(csk),C Terminal Src Kinase,CSK Tyrosine Protein Kinase,CSK src,CSK, Tyrosine-Protein Kinase,Carboxy Terminal Src Kinase,Kinase CSK, Tyrosine-Protein,Kinase c-src, Protein-Tyrosine,Kinase, C-Terminal Src,Kinase, CSK Tyrosine-Protein,Kinase, Carboxy-Terminal Src,Kinase, c-src,Kinase, c-src Tyrosine,Protein Tyrosine Kinase C Terminal Src Kinase,Protein Tyrosine Kinase c src,Src Kinase, C-Terminal,Src Kinase, Carboxy-Terminal,Tyrosine Kinase, c-src,Tyrosine Protein Kinase CSK,Tyrosine-Protein Kinase, CSK,c src Kinase,c src Tyrosine Kinase,c-src, Protein-Tyrosine Kinase
D000595	Amino Acid Sequence	The order of amino acids as they occur in a polypeptide chain. This is referred to as the primary structure of proteins. It is of fundamental importance in determining PROTEIN CONFORMATION.	Protein Structure, Primary,Amino Acid Sequences,Sequence, Amino Acid,Sequences, Amino Acid,Primary Protein Structure,Primary Protein Structures,Protein Structures, Primary,Structure, Primary Protein,Structures, Primary Protein
D013045	Species Specificity	The restriction of a characteristic behavior, anatomical structure or physical system, such as immune response; metabolic response, or gene or gene variant to the members of one species. It refers to that property which differentiates one species from another but it is also used for phylogenetic levels higher or lower than the species.	Species Specificities,Specificities, Species,Specificity, Species
D013379	Substrate Specificity	A characteristic feature of enzyme activity in relation to the kind of substrate on which the enzyme or catalytic molecule reacts.	Specificities, Substrate,Specificity, Substrate,Substrate Specificities
D015800	Protozoan Proteins	Proteins found in any species of protozoan.	Proteins, Protozoan
D016415	Sequence Alignment	The arrangement of two or more amino acid or base sequences from an organism or organisms in such a way as to align areas of the sequences sharing common properties. The degree of relatedness or homology between the sequences is predicted computationally or statistically based on weights assigned to the elements aligned between the sequences. This in turn can serve as a potential indicator of the genetic relatedness between the organisms.	Sequence Homology Determination,Determination, Sequence Homology,Alignment, Sequence,Alignments, Sequence,Determinations, Sequence Homology,Sequence Alignments,Sequence Homology Determinations