Mutation of the hydrophobic motif in a phosphorylation-deficient mutant renders protein kinase C delta more apoptotically active.
Protein kinase C delta (PKCdelta) is one of the important isoforms of PKCs that regulate various cellular processes, including cell survival and apoptosis. Studies have shown that activation of PKCdelta is correlated with apoptosis in various cell types, depending upon various stimuli. Phosphorylation of Thr505, Ser643 and Ser662 is crucial in activation of PKCdelta. Furthermore, phosphorylation of tyrosine residues, in particular that of Tyr311, is associated with PKCdelta activation and induction of apoptosis. Here, we generated a hydrophobic motif phosphorylation-deficient mutant of PKCdelta (PKCdelta-S662A) by mutating Ser662 to Ala, and studied the effect of this mutation in inducing apoptosis in L929 murine fibroblasts. We report that this mutation renders PKCdelta apoptotically more active. Furthermore, we found that the mutant PKCdelta-S662A is tyrosine-phosphorylated and translocated to the membrane faster than its wild-type counterpart.
Karmacharya
Mrigendra B
MB
Biomedical Research Center for Signal Transduction Networks, Department of Chemistry, Inha University, Incheon, Korea.
Jang
Jung-Ie
JI
Lee
Yoon-Jin
YJ
Lee
Yun-Sil
YS
Soh
Jae-Won
JW
D020816:Amino Acid Motifs / Q000502:physiology; D019943:Amino Acid Substitution; D000818:Animals; D017209:Apoptosis / Q000502:physiology*; D002460:Cell Line; D002462:Cell Membrane / Q000201:enzymology* / Q000235:genetics; D004789:Enzyme Activation / Q000235:genetics; D005347:Fibroblasts / Q000166:cytology / Q000201:enzymology*; D057927:Hydrophobic and Hydrophilic Interactions; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D051379:Mice; D020125:Mutation, Missense; D010766:Phosphorylation / Q000235:genetics; D051745:Protein Kinase C-delta / Q000235:genetics / Q000378:metabolism*; D021381:Protein Transport / Q000502:physiology
D007527:Isoenzymes; D051745:Protein Kinase C-delta