title: cGMP-dependent protein kinase I promotes cell apoptosis through hyperactivation of death-associated protein kinase 2.
abstract: cGMP-dependent protein kinase-I (cGK-I) induces apoptosis in various cancer cell lines. However, the signaling mechanisms involved remain unknown. Using protein microarray technology, we identified a novel cGK substrate, death-associated protein kinase 2 (DAPK2), which is a Ca(2+)/calmodulin-regulated serine/threonine kinase. cGK-I phosphorylated DAPK2 at Ser(299), Ser(367) and Ser(368). Interestingly, a phospho-mimic mutant, DAPK2 S299D, significantly enhanced its kinase activity in the absence of Ca(2+)/calmodulin, while a S367D/S368D mutant did not. Overexpression of DAPK2 S299D also resulted in a twofold increase in apoptosis of human breast cancer MCF-7 cells as compared with wild-type DAPK2. These results suggest that DAPK2 is one of the targets of cGK-I in apoptosis induction.
authors.affiliation: Department of Biological Science and Technology, The University of Tokushima Graduate School, Tokushima 770-8506, Japan.
authors.forename: Kinuka
authors.initials: K
authors.lastname: Isshiki
authors.forename: Shinya
authors.initials: S
authors.lastname: Matsuda
authors.forename: Akihiko
authors.initials: A
authors.lastname: Tsuji
authors.forename: Keizo
authors.initials: K
authors.lastname: Yuasa
mesh_terms: D000818:Animals; D017209:Apoptosis; D051017:Apoptosis Regulatory Proteins / Q000235:genetics / Q000378:metabolism*; D019556:COS Cells; D017871:Calcium-Calmodulin-Dependent Protein Kinases / Q000235:genetics / Q000378:metabolism*; D045744:Cell Line, Tumor; D002522:Chlorocebus aethiops; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases / Q000378:metabolism*; D064550:Death-Associated Protein Kinases; D004789:Enzyme Activation; D006801:Humans; D051379:Mice; D009154:Mutation; D010766:Phosphorylation; D040081:Protein Array Analysis; D012694:Serine / Q000235:genetics / Q000378:metabolism; D013379:Substrate Specificity
chemical_list: D051017:Apoptosis Regulatory Proteins; D012694:Serine; C579104:DAPK2 protein, human; D064550:Death-Associated Protein Kinases; C579103:dapk2 protein, mouse; D062965:Cyclic GMP-Dependent Protein Kinase Type I; D017869:Cyclic GMP-Dependent Protein Kinases; C569718:PRKG1 protein, human; C569720:Prkg1 protein, mouse; D017871:Calcium-Calmodulin-Dependent Protein Kinases