Probing the Dynamic Properties of the Kinome

Dear Colleagues,

The human kinome is a highly interconnected network of ~500 kinases that controls a myriad of cellular events through reversible phosphorylation. This network is regulated by multiple inputs including second messengers, activation loop phosphorylation, feedback and cross-talk phosphorylation events, transcriptional modulation, post-translational modifications, dimerization, targeted degradation and other mechanisms. Aberrant activation of kinases, by mutations or over-expression, and the importance of these events to cell growth regulation are well documented in cancer biology. Not surprisingly, a large number of kinase inhibitors are in clinical trials for treatment of a variety of cancers and other diseases. However, efforts to study the kinome through the study of isolated kinase pathways have resulted in limited knowledge regarding the function of the kinome as an entity. New technologies have emerged that allow better characterization of kinome behavior ‘en masse’. The application of these approaches has lead to the realization that the kinome is highly dynamic and is capable of responding or “reprogramming” to growth or inhibitory signals. Identifying these homeostatic mechanisms will be important to understanding the action of targeted kinase inhibitors, particularly those that fail in the clinic for unknown reasons. The objective of this Special Issue is to explore recent studies designed to study the kinome and to evaluate the insight gained from this research.

Prof. Dr. Lee M. Graves
Guest Editor

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