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Sci. Signal., 21 December 2010
Vol. 3, Issue 153, p. rs4
[DOI: 10.1126/scisignal.2001182]


Editor's Summary

Holistic Approach
Protein kinases and phosphatases make attractive targets for therapies. Although various such enzymes have been characterized individually in vitro, an understanding of their roles in vivo, in the context of the entire network of kinases and phosphatases, is lacking. Indeed, inadequate knowledge of the downstream, indirect consequences of targeting a particular enzyme has led to the discontinuation of potential therapies. Bodenmiller et al. (listen to the accompanying Podcast) individually targeted most of the kinases and phosphatases in yeast, and they performed phosphoproteomic analysis of the effects of these deletions or mutations on the cellular phosphorylation network. They found that the network was surprisingly robust to perturbations in individual enzymes and that a large number of changes occurred in phosphoproteins that were not direct substrates of the targeted kinase or phosphatase. This approach should serve as a starting point toward understanding the complexity of phosphorylation regulation in yeast and other organisms.

Citation: B. Bodenmiller, S. Wanka, C. Kraft, J. Urban, D. Campbell, P. G. Pedrioli, B. Gerrits, P. Picotti, H. Lam, O. Vitek, M.-Y. Brusniak, B. Roschitzki, C. Zhang, K. M. Shokat, R. Schlapbach, A. Colman-Lerner, G. P. Nolan, A. I. Nesvizhskii, M. Peter, R. Loewith, C. von Mering, R. Aebersold, Phosphoproteomic Analysis Reveals Interconnected System-Wide Responses to Perturbations of Kinases and Phosphatases in Yeast. Sci. Signal. 3, rs4 (2010).

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