Note to users. If you're seeing this message, it means that your browser cannot find this page's style/presentation instructions -- or possibly that you are using a browser that does not support current Web standards. Find out more about why this message is appearing, and what you can do to make your experience of our site the best it can be.

Subscribe

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).

Read the Full Text


THIS ARTICLE HAS BEEN CITED BY OTHER ARTICLES:
Protein Kinases Curb Cell Death.
O. Filhol and C. Cochet (2011)
Science Signaling 4, pe26
   Abstract »    Full Text »    PDF »

To Advertise     Find Products


Science Signaling. ISSN 1937-9145 (online), 1945-0877 (print). Pre-2008: Science's STKE. ISSN 1525-8882