Identification of a novel antiapoptotic human protein kinase C delta isoform, PKCdeltaVIII in NT2 cells.

Protein kinase C (PKC) δ plays an important role in cellular proliferation and apoptosis where it is involved in the caspase-3 mediated apoptotic pathway. Cleavage of PKCδI by caspase-3 releases a catalytically active C-terminal fragment that is sufficient to induce apoptosis. In this paper, we identified a novel human PKCδ isozyme, PKCδVIII (Genbank accession number DQ516383) in human teratocarcinoma (NT2) cells that differentiate into hNT neurons upon retinoic acid (RA) treatment. Expression of PKCδVIII was confirmed by real-time RT-PCR analysis, and we observed that after an initial peak at 24 h following RA treatment, its expression gradually declined with prolonged RA treatment. PKCδVIII is generated via the utilization of an alternative 5‘ splice site, and this results in an insertion of 31 amino acids in the caspase-3 recognition sequence DMQD. The function of PKCδVIII was examined by subcloning it into an expression vector and raising an antibody specific to PKCδVIII. Using in vivo and in vitro as...