Discovery and exploitation of inhibitor-resistant aurora and polo kinase mutants for the analysis of mitotic networks.

ABSTRACT: The Aurora and Polo-like kinases are central components of mitotic signaling pathways, and recent evidence suggests that substantial cross-talk exists between Aurora A and Plk1. In addition to their validation as novel anticancer agents, small molecule kinase inhibitors are increasingly important tools to help dissect clinically relevant protein phosphorylation networks. However, one major problem associated with kinase inhibitors is their promiscuity toward "off-target" members of the kinome, which makes interpretation of data obtained from complex cellular systems challenging. Additionally, the emergence of inhibitor resistance in patients makes it clear that an understanding of resistance mechanisms is essential to inform drug design. In this study, we exploited structural knowledge of

SUBMITTER: Scutt PJ 

PROVIDER: S-EPMC2708884 | biostudies-literature | 2009 Jun

REPOSITORIES: biostudies-literature