A point mutation at phenylalanine 663 abolishes protein kinase C alpha‘s ability to translocate to the perinuclear region and activate phospholipase D1
Previous research showed that protein kinase C alpha(PKC alpha) 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 PKC alpha is essential for its translocation. A point mutation (F663D) completely blocked PKC alpha's binding to and activation of phospholipase D1. Further studies showed that deletion of the C-terminal nine amino acids of PKC alpha 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 PKC alpha is required for its relocation from plasma membrane to the perinuclear region. (c) 2005 Elsevier Inc. All rights reserved.