title: A peptide-based target screen implicates the protein kinase CK2 in the global regulation of caspase signaling.
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.
authors.affiliation: Department of Biochemistry, University of Western Ontario, London, Ontario, Canada N6A 5C1.
authors.forename: James S
authors.initials: JS
authors.lastname: Duncan
authors.forename: Jacob P
authors.initials: JP
authors.lastname: Turowec
authors.forename: Kelly E
authors.initials: KE
authors.lastname: Duncan
authors.forename: Greg
authors.initials: G
authors.lastname: Vilk
authors.forename: Chenggang
authors.initials: C
authors.lastname: Wu
authors.forename: Bernhard
authors.initials: B
authors.lastname: Lüscher
authors.forename: Shawn S-C
authors.initials: SS
authors.lastname: Li
authors.forename: Greg B
authors.initials: GB
authors.lastname: Gloor
authors.forename: David W
authors.initials: DW
authors.lastname: Litchfield
mesh_terms: D000595:Amino Acid Sequence; D017209:Apoptosis; D047390:Casein Kinase II / Q000378:metabolism*; D020169:Caspases / Q000378:metabolism*; D006868:Hydrolysis; D013058:Mass Spectrometry; D010766:Phosphorylation; D015398:Signal Transduction; D013379:Substrate Specificity
chemical_list: D047390:Casein Kinase II; D020169:Caspases