A point mutation at phenylalanine 663 abolishes protein kinase Cα's ability to translocate to the perinuclear region and activate phospholipase D1

Previous research showed that protein kinase Cα (PKCα) translocated to the perinuclear region and activated phospholipase D1, but the mechanism involved was not clear. Here, we provide evidence that Phe 663 (the 10th amino acid from C-terminus) of PKCα is essential for its translocation. A point mutation (F663D) completely blocked PKCα's binding to and activation of phospholipase D1. Further studies showed that deletion of the C-terminal nine amino acids of PKCα did not alter its translocation to the perinuclear region but deletion of the C-terminal 10 amino acids and the F663D mutation abolished this translocation. The F663D mutant was found to be resistant to dephosphorylation, which might account for its inability to translocate to the perinuclear region and activate PLD1, since dephosphorylation of PKCα is required for its relocation from plasma membrane to the perinuclear region.