New Kinase Matchmaker

With help from ultraviolet light, chemists have developed a method to identify substrates of kinase enzymes, which catalyze protein phosphorylation reactions in cells (Angew. Chem. Int. Ed., DOI: 10.1002/anie.200905244). Pinning down kinase-substrate interactions is important for understanding the signaling networks that underlie cancers and other diseases, and several research teams have developed cross-linking reagents for that purpose. Now, Sujit Suwal and Mary Kay H. Pflum of Wayne State University have developed the first reagent that requires phosphorylation to happen before kinase-substrate cross-linking can occur. The reagent, an ATP analog, has a light-activated aryl azide group attached to the end of its trio of phosphates. During phosphorylation, shining UV light activates the reagent to couple the substrate and kinase. So far, the cross-linking works with a variety of known kinases and their peptide substrates, as well as for one full-length protein substrate. Paired with mass spectrometry, the technique also reveals the precise amino acid sites of phosphorylation, Suwal and Pflum note.