cGMP-dependent protein kinase I promotes cell apoptosis through hyperactivation of death-associated protein kinase 2

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• 作者：Kinuka Isshiki ; Shinya Matsuda ; Akihiko Tsuji ; Keizo Yuasa ; ^{yuasa@bio.tokushima-u.ac.jp}
• 关键词：cGK ; cGMP-dependent protein kinase ; DAPK ; death-associated protein kinase ; NO ; nitric oxide ; CaM ; calmodulin ; MLC ; myosin light chain ; GST ; glutathione S-transferase ; PBS ; phosphate-buffered saline ; GFP ; green fluorescent protein ; APC ; adenomatous polypos
• 刊名：Biochemical and Biophysical Research Communications
• 出版年：2012
• 期刊代码：159_0006291x
• 类别：bio
• 出版时间：1 June, 2012
• 卷：422
• 期：2
• 页码：280-284
• 文件大小：502 K

摘要

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 Ca²⁺/calmodulin-regulated serine/threonine kinase. cGK-I phosphorylated DAPK2 at Ser²⁹⁹, Ser³⁶⁷ and Ser³⁶⁸. Interestingly, a phospho-mimic mutant, DAPK2 S299D, significantly enhanced its kinase activity in the absence of Ca²⁺/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.