Characterization of a Chemical Affinity Probe Targeting Akt Kinases

Pachl F, Plattner P, Ruprecht B, Medard G, Sewald N, Kuster B (2013)
Journal of Proteome Research 12(8): 3792-3800.

Zeitschriftenaufsatz | Veröffentlicht | Englisch
 
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Autor*in
Pachl, Fiona; Plattner, Patrik; Ruprecht, Benjamin; Medard, Guillaume; Sewald, NorbertUniBi ; Kuster, Bernhard
Abstract / Bemerkung
Protein kinases are key regulators of cellular processes, and aberrant function is often associated with human disease. Consequently, kinases represent an important class of therapeutic targets and about 20 kinase inhibitors (KIs) are in clinical use today. Detailed knowledge about the selectivity of KIs is important for the correct interpretation of their pharmacological and systems biological effects. Chemical proteomic approaches for systematic kinase inhibitor selectivity profiling have emerged as important molecular tools in this regard, but the coverage of the human kinome is still incomplete. Here, we describe a new affinity probe targeting Akt and many other members of the AGC kinase family that considerably extends the scope of KI profiling by chemical proteomics. In combination with the previously published kinobeads, the synthesized probe was applied to selectivity profiling of the Akt inhibitors GSK690693 and GSK2141795 in human cancer cells. The results confirmed the inhibition of all Akt isoforms and of a number of known as well as CDC42BPB as a novel putative target for GSK690693. This work also established, for the first time, the kinase selectivity profile of the clinical phase I drug GSK2141795 and identified PRKG1 as a low nanomolar kinase target as well as the ATP-dependent 5'-3' DNA helicase ERCC2 as a potential new non-kinase off-target.
Stichworte
chemical proteomics; kinobeads; Akt; mass spectrometry
Erscheinungsjahr
2013
Zeitschriftentitel
Journal of Proteome Research
Band
12
Ausgabe
8
Seite(n)
3792-3800
ISSN
1535-3893
eISSN
1535-3907
Page URI
https://pub.uni-bielefeld.de/record/2625906

Zitieren

Pachl F, Plattner P, Ruprecht B, Medard G, Sewald N, Kuster B. Characterization of a Chemical Affinity Probe Targeting Akt Kinases. Journal of Proteome Research. 2013;12(8):3792-3800.
Pachl, F., Plattner, P., Ruprecht, B., Medard, G., Sewald, N., & Kuster, B. (2013). Characterization of a Chemical Affinity Probe Targeting Akt Kinases. Journal of Proteome Research, 12(8), 3792-3800. doi:10.1021/pr400455j
Pachl, Fiona, Plattner, Patrik, Ruprecht, Benjamin, Medard, Guillaume, Sewald, Norbert, and Kuster, Bernhard. 2013. “Characterization of a Chemical Affinity Probe Targeting Akt Kinases”. Journal of Proteome Research 12 (8): 3792-3800.
Pachl, F., Plattner, P., Ruprecht, B., Medard, G., Sewald, N., and Kuster, B. (2013). Characterization of a Chemical Affinity Probe Targeting Akt Kinases. Journal of Proteome Research 12, 3792-3800.
Pachl, F., et al., 2013. Characterization of a Chemical Affinity Probe Targeting Akt Kinases. Journal of Proteome Research, 12(8), p 3792-3800.
F. Pachl, et al., “Characterization of a Chemical Affinity Probe Targeting Akt Kinases”, Journal of Proteome Research, vol. 12, 2013, pp. 3792-3800.
Pachl, F., Plattner, P., Ruprecht, B., Medard, G., Sewald, N., Kuster, B.: Characterization of a Chemical Affinity Probe Targeting Akt Kinases. Journal of Proteome Research. 12, 3792-3800 (2013).
Pachl, Fiona, Plattner, Patrik, Ruprecht, Benjamin, Medard, Guillaume, Sewald, Norbert, and Kuster, Bernhard. “Characterization of a Chemical Affinity Probe Targeting Akt Kinases”. Journal of Proteome Research 12.8 (2013): 3792-3800.

9 Zitationen in Europe PMC

Daten bereitgestellt von Europe PubMed Central.

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