A phosphorylation-deficient mutant of PKCδ in the V5 region is more active in inducing apoptosis in murine fibroblasts

초록

rotein Kinase C δ (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 as a pro- as well as anti-apoptotic protein in various cell lines. Induction of apoptosis in these various cell lines has been found to correlate with the activation of PKCδ. For the catalytic activity of PKCδ, phosphorylation of serine, threonine and tyrosine residues in various regions play important roles, 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 of PKCδ, in inducing apoptosis in murine fibroblast cell line L929. For this purpose, we generated hydrophobic motif phosphorylation-deficient mutant of PKCδ and compared the catalytic activity of this mutant with wild type PKCδ. We report that this phosphorylation-deficient mutant is catalytically more active and that the mutant induces more apoptosis than wild type PKCδ in L929 cells. Furthermore, this mutant was found to translocate to the membrane faster than the wild type isoform.