%0 Journal Article
%T Clustering of phosphorylation site recognition motifs can be exploited to predict the targets of cyclin-dependent kinase
%A Alan M Moses
%A Jean-Karim H¨¦rich¨¦
%A Richard Durbin
%J Genome Biology
%D 2007
%I BioMed Central
%R 10.1186/gb-2007-8-2-r23
%X Protein kinases are ubiquitous components of cellular signalling networks [1]. A relatively well understood example is the network that controls progression of the cell cycle, where cyclin-dependent kinases (CDKs) couple with various cyclins over the cell cycle to regulate critical processes [2-4]. Despite their biological and medical importance, relatively few direct, in vivo targets of these kinases have been identified conclusively, because experimental techniques are difficult and time consuming [1,5]. With the availability of databases of protein sequences, computational methods provide an alternative approach [6,7].Kinase substrates often have short, degenerate sequence motifs surrounding the phosphorylated residue [8]. Putative target residues can be predicted by searching for matches to the consensus for a particular kinase. For example, CDK substrates often contain S/T-P-X-R/K where X represents any amino acid, and S/T represents the phosphorylated serine or threonine [9,10]. Because of the low specificity of the CDK consensus, however, databases of protein sequences are expected to contain large numbers of matches by chance. Therefore, many of the matches in protein sequences are likely to be false-positive predictions. Consistent with this, when 553 Saccharomyces cerevisiae proteins with at least one match to the CDK consensus were tested in a high-throughput kinase assay, only 32% (178) were found to be substrates [11]. Furthermore, in some cases characterized CDK substrates are phosphorylated at residues matching only a minimal consensus S/T-P [12]; considering these weak matches would probably lead to even larger numbers of false positives.Characterized CDK targets may be phosphorylated at multiple residues (for instance, see the report by Lees and coworkers [13]). Recent studies of several CDK target proteins in S. cerevisiae have shown that these multiple phosphorylations can regulate stability [12], protein interaction [14,15], or localization [16].
%U http://genomebiology.com/2007/8/2/R23