Functional analysis of disease-associated protein kinases using phosphoproteomic technologies including Phos-tag

Abstract

Protein phosphorylation is one of the most widespread types of post-translational modifications in eukaryotes and can regulate diverse properties of proteins. Protein kinases are encoded by over 500 genes in the human genome and play critical roles in various signaling pathways. In fact, many diseases are associated with mutations in protein kinases. To fully and therapeutically understand the complex signaling networks, it is essential to develop analytical strategies for the global identification and functional characterization of in vivo substrates of individual protein kinases. Recent advances in various phosphoproteomic technologies such as Phos-tag Western blotting have enabled efficient and detailed analysis of protein kinase substrates. Here, we describe cellular functions of the newly identified substrates of three disease-associated protein kinases including ERK, PKD and PINK1.