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Sci. Signal., 10 May 2011
Vol. 4, Issue 172, p. ra30
[DOI: 10.1126/scisignal.2001682]

RESEARCH ARTICLES

A Peptide-Based Target Screen Implicates the Protein Kinase CK2 in the Global Regulation of Caspase Signaling

James S. Duncan1*, Jacob P. Turowec1*, Kelly E. Duncan1, Greg Vilk1, Chenggang Wu1, Bernhard Lüscher2, Shawn S.-C. Li1, Greg B. Gloor1, and David W. Litchfield1{dagger}

1 Department of Biochemistry, University of Western Ontario, London, Ontario, Canada N6A 5C1.
2 Institut fur Biochemie und Molekularbiologie, Medizinische Fakultät, Rheinisch-Westfalische Technische Hochschule, RWTH Aachen University, 52057 Aachen, Germany.

* These authors contributed equally to this work.

Abstract: The convergence of caspase and protein kinase signaling pathways has become increasingly evident, as illustrated by the protection of caspase substrates from cleavage upon undergoing phosphorylation at or near to their caspase recognition motifs. To investigate the global role of phosphorylation in the regulation of caspase signaling, we designed a peptide match program to identify sequences from the human proteome that contained overlapping recognition motifs for caspases and kinases. We identified the protein kinase CK2 as the most prominent kinase with a consensus site for phosphorylation that overlapped with caspase recognition motifs. We then evaluated potential targets of CK2 and caspases by combining peptide array target screens with identification of caspase substrates. We identified numerous shared candidate targets of CK2 and caspases, including procaspase-3, which functions at a level at which both intrinsic and extrinsic apoptotic signals converge. Together, these data support a role for CK2-dependent phosphorylation as a global mechanism for inhibiting caspase signaling pathways.

{dagger} To whom correspondence should be addressed. E-mail: litchfi{at}uwo.ca

Citation: J. S. Duncan, J. P. Turowec, K. E. Duncan, G. Vilk, C. Wu, B. Lüscher, S. S.- C. Li, G. B. Gloor, D. W. Litchfield, A Peptide-Based Target Screen Implicates the Protein Kinase CK2 in the Global Regulation of Caspase Signaling. Sci. Signal. 4, ra30 (2011).

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