Biological Consequences of Priming Phosphorylation in Cancer Development

Abstract

Abstract Multisite phosphorylations on a single polypeptide mediated by protein kinase(s) are commonly observed. In some cases, hierarchical phosphorylations occur when first prim- ing event triggers second processive phosphorylation. Hierarchal multisite phosphoryla- tion that is mediated by a priming kinase and a processive kinase is a fail-safe system that accurately regulates physiological processes, including cell cycle progression, survival, migration, metabolism, differentiation and stem cell renewal. Here, we summarize the findings of cancer-associated priming kinases (CK1 and DYRK family) and processive kinase (GSK3). GSK3 has an unusual ability to accurately regulate the wide variety of cellular processes via the priming phosphorylation of its substrates. Therefore, dysregu- lation of priming phosphorylation gives rise to pathological disorders such as cancer.