Protein domain microarrays as a platform to decipher signaling pathways and the histone code

Signal transduction is driven by protein interactions that are controlled by posttranslational modifications (PTM). Usually, protein domains are responsible for “reading” the PTM signal deposited on the interacting partners. Protein domain microarrays have been developed as a high throughput platform to facilitate the rapid identification of protein-protein interactions, and this approach has become broadly used in biomedical research. In this review, we will summarize the history, development and applications of this technique, including the use of protein domain microarrays in identifying both novel protein-protein interactions and small molecules that block these interactions. We will focus on the approaches we use in the Protein Array and Analysis Core – the PAAC – at MD Anderson Cancer Center. We will also address the technical limitations and discuss future directions.