The roles of cGMP-dependent protein kinase and its novel substrates in nervous system

1.CGK I在Ser299、Ser367和Ser368处使DAPK2磷酸化。模拟磷酸化的突变体DAPK2 S299D显著增强其活性，而S367D/S368D突变体则不能。此外，与野生型相比，DAPK2 S299D过表达导致人乳腺癌MCF7细胞的凋亡率显著增加。14-3-3S为DAPK2相互作用蛋白。DAPK2在其C端与Thr369的14-3-3S磷酸化相互作用，其活性被14-3-3S抑制。细胞周期蛋白A被鉴定为PCTK3的激活剂。CDK2与Cyclin A在胞核形成络合物，而PCTK3与Cyclin A在胞浆相互作用。

1. cGK I phosphorylated DAPK2 at Ser299, Ser367and Ser368. A phospho-mimic mutant DAPK2 S299D significantly enhanced its kinase activity, while a S367D/S368D mutant did not. Furthermore, overexpression of DAPK2 S299D resulted in a significant increase in apoptosis of human breast cancer MCF7 cells, compared with that of wild type.2. 14-3-3s were identified as DAPK2-interacting proteins. DAPK2 interacted with 14-3-3s viaphosphorylation of Thr369at its C-terminus, and its kinase activity was inhibited by 14 -3-3s.3. Cyclin A was identified as an activator of PCTK3. CDK2 is complexed with cyclin A in the nucleus, while PCTK3 interacted with cyclin A in the cytoplasm.