Mutation of the hydrophobic motif to phosphorylation-deficient mutant renders Protein Kinase C delta apoptotically more active

초록

Protein Kinase C (PKC) is a multi-gene subfamily of serine-threonine kinases comprising of at least ten isoforms which play important roles in multitudes of cellular processes as proliferation, differentiation, growth, and apoptosis. On the basis of the difference in the regulatory domain of the isoforms, PKC is divided into three classes, viz., cPKC, nPKC and aPKC. PKCδ is one of the important isoforms among the PKCs in regulating various cellular processes including cell survival and apoptosis. Activation of PKCδ is correlated with apoptosis in various cell types. Phosphorylation of Thr505, Ser643 and Ser662 are crucial in activation of PKCδ. Furthermore, phosphorylation of tyrosine residues, in particular that of Tyr311, is related with PKCδ activation and induction of apoptosis. Here, we mutated Ser662 to Ala and generated phosphorylation-deficient mutant of PKCδ (PKCδ-S662A) and studied the effect of this mutation in inducing apoptosis in L929 murine fibroblsasts. We report that this mutation renders PKCδ apoptotically more active. Furthermore, the mutant PKCδ-S662A is more tyrosine phosphorylated and translocated to the membrane faster than its wild type counterpart.