Protein microarrays for genome-wide posttranslational modification analysis

Protein microarray technology has emerged as a powerful tool for comparing binding interactions, expression level, substrate specificities, and posttranslational modifications (PTMs) of different proteins in a parallel and high-throughput manner. The ability to immobilize proteins to a solid surface and register the specific address of each protein has bridged major limitations for investigating the proteome in biological samples, namely, the wide dynamic range of protein concentrations and the perturbation of the physical and chemical properties of proteins by their modification. Recent advances introduced the use of functional mammalian cell extracts to assay PTMs under different cellular conditions. This assay offers a new approach for performing large-scale complex biochemical analysis of protein modifications. Here, we review studies of PTM profiling using protein microarrays and discuss the limitations and potential applications of the system. We believe that the information generated from such proteomic studies may be of significant value in our elucidation of the molecular mechanisms that govern human physiology.