Chemical approaches towards unravelling kinase-mediated signalling pathways

Hodgson, D.R.W.; Schröder, M.

Abstract

Protein kinases control the function of about one third of cellular proteins by catalysing the transfer of the γ-phosphate group of ATP onto their substrate proteins. Protein phosphatases counter this action and also control the activation status of many kinases. Cellular responses to environmental changes, or signalling events, temporarily tilt the balance of protein phosphorylation and dephosphorylation to one side or the other. The identification of protein-kinase–substrate pairs and substrate–phosphatase pairs is critical to understanding cell function and how cells respond to environmental changes. Identification of these substrate–enzyme pairs is non-trivial, because of the structural and mechanistic conservation of the catalytic cores of protein kinases. In this tutorial review we review recent progress towards identifying protein-kinase–substrate pairs by emphasising the use of chemical genetics and purpose-designed ATP analogues that target one particular protein kinase. In addition, we discuss activity-based chemical profiling approaches, based on ATP analogues, for the detection of active kinases.

Citation

Hodgson, D., & Schröder, M. (2011). Chemical approaches towards unravelling kinase-mediated signalling pathways. Chemical Society Reviews, 40(3), 1211-1223. https://doi.org/10.1039/c0cs00020e

• Journal Article Type: Article
• Publication Date: Mar 1, 2011
• Deposit Date: May 17, 2013
• Publicly Available Date: May 22, 2013
• Journal: Chemical Society Reviews
• Print ISSN: 0306-0012
• Electronic ISSN: 1460-4744
• Publisher: Royal Society of Chemistry
• Peer Reviewed: Peer Reviewed
• Volume: 40
• Issue: 3
• Pages: 1211-1223
• DOI: https://doi.org/10.1039/c0cs00020e
• Public URL: https://durham-repository.worktribe.com/output/1484181