The role of hydrophobic motif phosphorylation in the V5 region of Protein Kinase C delta in its activation and subsequent induction of apoptosis in murine fibroblasts

초록

Protein Kinase C delta (PKCδ), one of the important isoforms of PKC, a multi-gene sub-family of serine-threonine kinases consisting of at least 10 isoforms, has been well studied and its role as a pro- as well as anti-apoptotic protein in various cell lines has been established. For its catalytic activity, phosphorylation of serine, threonine and tyrosine residues in various regions are important, especially phosphorylation status of Thr505 in the activation loop, Ser643 in the turn motif, Ser662 in the hydrophobic motif and Tyr311/Tyr332 in the V3 region are crucial. Here, we intended to study the role of the hydrophobic motif, located in the V5 region, in the membrane translocation and activation of PKCδ, and the subsequent induction of apoptosis. For this we generated hydrophobic motif phoshorylation-deficient mutant of PKCδ and compared the catalytic activity of this mutant with wild type PKCδ in murine fibroblast cell line L929. We report that this mutant is catalytically more active and it induced more apoptosis than wild type PKCδ in L929 cells. These results further underscore the importance of the hydrophobic motif in the V5 region of the isoform in its apoptotic activity.