Characterization of the phosphorylation sites of protein kinase C delta

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 such as proliferation, differentiation, growth, and apoptosis. On the basis of the structural difference in the regulatory domain of the isoforms, PKC is divided into three classes (classical, novel and atypical PKCs). PKC delta is one of the important isoforms among the PKCs in regulating various cellular processes including cell survival and apoptosis. Studies have shown that activation of PKC delta is correlated with apoptosis in various cell types depending upon various stimuli. Phosphorylation of Thr505, Ser643 and Ser662 is crucial in activation of PKC delta. Furthermore, phosphorylation of tyrosine residues, in particular, that of Tyr311 is related with PKC delta activation and induction of apoptosis. We mutated Serine 662 to Alanine and generated hydrophobic motif phosphorylation-deficient mutant of PKC delta and studied the effect of this mutation in inducing apoptosis in L929 murine fibroblsasts. We report that this mutation renders PKC delta apoptotically more active.