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

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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.