The role of protein phosphatases type 2 C in neuronal apoptosis

In previous work we found out that the protein phosphatase type 2C (PP2C) could be activated by low molecular weight compounds which had to fulfill special requirements. The activators had to be lipophilic, acidic and oxidizable and they had to have a special configuration, for instance only the cis- but not the trans-configuration of oleic acid was effective. The position of the double bond was crucial as well. In addition, we could also demonstrate that the activation was true only for PP2C. Other phosphatases tested such as PP1, PP2A, PP2B, acid and alkaline phosphatases and a tyrosine phosphatase were not activated or even inhibited by these compounds. Surprisingly, the compounds which massively activated PP2C also significantly induced apoptotic damage of cultured neurons obtained from embryonic chick telencephalon. There was a striking correlation between activation of PP2C and induction of apoptosis and the question arose whether and how PP2C could act on the apoptotic cascades. Which protein from the signaling transduction of apoptosis could be dephosphorylated by this phosphatase with the consequence to cause apoptosis? In principle, there are several proteins which could be looked for. The pro-apoptotic oncogene Bad is a candidate of the first choice because it is distinctly involved in neuronal damage and protection.