Phosphoinositide-dependent kinase-1 (PDK1) mediates activation of many AGC kinases by docking onto a phosphorylated hydrophobic motif located C-terminal of the catalytic domain in the AGC kinase. The interaction shifts PDK1 into a conformation with increased catalytic activity and leads to autophosphorylation of PDK1. We demonstrate here that addition of a hydrophobic motif peptide increases the catalytic activity of PDK1 orthologues from Homo sapiens, Aplysia californica, Arabidopsis thaliana, Schizosaccharomyces pombe (ksg1), and Saccharomyces cerevisiae (Pkh1 and Pkh2) 2- to 12-fold. Furthermore, the hydrophobic motif peptide increases autophosphorylation of PDK1 from Homo sapiens, S. pombe, and S. cerevisiae (Phk2). Our results suggest that PDK1 interaction and activation by the hydrophobic motif of AGC kinases is a central mechanism in PDK1 function, which is conserved during eukaryotic evolution.
|Evidence ID||Analyze ID||Interactor||Interactor Systematic Name||Interactor||Interactor Systematic Name||Type||Assay||Annotation||Action||Modification||Phenotype||Source||Reference||Note|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Gene Ontology Term||Gene Ontology Term ID||Qualifier||Aspect||Method||Evidence||Source||Assigned On||Annotation Extension||Reference|
|Evidence ID||Analyze ID||Gene||Gene Systematic Name||Phenotype||Experiment Type||Experiment Type Category||Mutant Information||Strain Background||Chemical||Details||Reference|
|Evidence ID||Analyze ID||Regulator||Regulator Systematic Name||Target||Target Systematic Name||Experiment||Assay||Construct||Conditions||Strain Background||Reference|