Abstract
Protein kinase-mediated phosphorylation is among the most important post-translational modifications. However, few phosphorylation sites have been experimentally identified for most species, making it difficult to determine the degree to which phosphorylation sites are conserved. The goal of this study was to use computational methods to characterize the conservation of human phosphorylation sites in a wide variety of eukaryotes. Using experimentally-determined human sites as input, homologous phosphorylation sites were predicted in all 432 eukaryotes for which complete proteomes were available. For each pair of species, we calculated phosphorylation site conservation as the number of phosphorylation sites found in both species divided by the number found in at least one of the two species. A clustering of the species based on this conservation measure was concordant with phylogenies based on traditional genomic measures. For a subset of the 432 species, phosphorylation site conservation was compared to conservation of both protein kinases and proteins in general. Protein kinases exhibited the highest degree of conservation, while general proteins were less conserved and phosphorylation sites were least conserved. Although preliminary, these data tentatively suggest that variation in phosphorylation sites may play a larger role in explaining phenotypic differences among organisms than differences in the complements of protein kinases or general proteins.
Highlights
IntroductionProtein kinases play a critical role in regulating cellular processes by catalyzing the phosphorylation of amino acid residues (usually serine, threonine, or tyrosine), which may activate, deactivate, or change the activity of the target protein [1, 2]
Protein kinases play a critical role in regulating cellular processes by catalyzing the phosphorylation of amino acid residues, which may activate, deactivate, or change the activity of the target protein [1, 2]
Most eukaryotic genomes encode a large number of protein kinases; for example, the human genome encodes more than 500 [2], while the Arabidopsis thaliana genome encodes more than 1000 [3]
Summary
Protein kinases play a critical role in regulating cellular processes by catalyzing the phosphorylation of amino acid residues (usually serine, threonine, or tyrosine), which may activate, deactivate, or change the activity of the target protein [1, 2]. Moses et al examined the evolution of sites phosphorylated by cyclin-dependent kinases in proteins comprising the pre-replicative complex (a set of interacting proteins involved in DNA replication) in a number of closelyand distantly-related organisms [6] They found that pre-replicative complex components often contained clusters of cyclin-dependent kinase consensus sites, the presence or position of individual sites were often poorly conserved, and that differences in these sites were associated with regulatory changes. The authors analyzed how often these discrepancies can be attributed to factors like false negatives and false positives in experimentally identifying sites, as well as to non-functional sites From this analysis, they estimated that approximately 5% of the sites that were conserved at the sequence level, but were known to be phosphorylated in only one of the two species, represented sites that were truly differentially regulated between the two species
Sign-in/Register to view highlights & summary Sign-in/Register to access full text options 
Talk to us
Join us for a 30 min session where you can share your feedback and ask us any queries you have
Schedule a callDisclaimer: All third-party content on this website/platform is and will remain the property of their respective owners and is provided on "as is" basis without any warranties, express or implied. Use of third-party content does not indicate any affiliation, sponsorship with or endorsement by them. Any references to third-party content is to identify the corresponding services and shall be considered fair use under The CopyrightLaw.
