Chemical approaches towards unravelling kinase-mediated signalling pathways

Hodgson, D.R.W.; Schröder, M.

doi:10.1039/c0cs00020e

Chemical approaches towards unravelling kinase-mediated signalling pathways

Hodgson, D.R.W.; Schröder, M.

Authors

Professor David Hodgson d.r.w.hodgson@durham.ac.uk
Professor

M. Schröder

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