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Fulfilling the Krebs and Beavo criteria for studying protein phosphorylation in the era of mass spectrometry-driven kinome research.

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Rider, Mark H. [UCL] Waelkens, Etienne Derua, Rita Vertommen, Didier [UCL]

The reversible phosphorylation of proteins controls virtually all aspects of cell function. However, in order to establish that the phosphorylation of a protein by a particular protein kinase is of physiological relevance, a series of criteria (proposed by Krebs & Beavo, 1979 ) should be satisfied. Surprisingly, amongst the thousands of protein kinase targets that have been reported in the literature, there are not so many for which there is good evidence for phosphorylation having functional consequences in vivo. Here we review the approaches that can be used to establish physiologically important protein phosphorylation according to the Krebs and Beavo criteria, taking as an example heart 6-phosphofruco-2-kinase phosphorylation-induced activation by insulin. We also point out the pitfalls of the various techniques that can be used to implicate the involvement of a particular protein kinase in a biological response. Lastly, we discuss the use of mass spectrometry techniques to search for new protein kinase targets, bearing in mind that each new target found would have to be validated by the criteria before being considered as a bona fide protein kinase substrate.

Document type Article de périodique (Journal article) – Journal Article, Research Support, Non-U.S. Gov't, Review
Access type Accès restreint
Publication date 2009
Journal information "Archives of physiology and biochemistry" - Vol. 115, no. 5, p. 298-310 (2009)
Peer reviewed yes
issn 1381-3455
e-issn 1744-4160
Publication status Publié
Affiliation UCL - MD/BICL - Département de biochimie et de biologie cellulaire
MESH Subject Substrate Specificity ; Rats ; Proteins - metabolism ; Phosphorylation ; Phosphofructokinase-2 - metabolism ; Myocardium - metabolism ; Mice ; Mass Spectrometry - methods ; Insulin - metabolism ; Humans ; Animals
Links
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Bibliographic reference Rider, Mark H. ; Waelkens, Etienne ; Derua, Rita ; Vertommen, Didier. Fulfilling the Krebs and Beavo criteria for studying protein phosphorylation in the era of mass spectrometry-driven kinome research.. In: Archives of physiology and biochemistry, Vol. 115, no. 5, p. 298-310 (2009)
Permanent URL http://hdl.handle.net/2078.1/28559