Protein kinase Cζ regulates phospholipase D activity in rat-1 fibroblasts expressing the α1A adrenergic receptor -: art. no. 4

Background: Phenylephrine (PHE), an alpha(1) adrenergic receptor agonist, increases phospholipase D (PLD) activity, independent of classical and novel protein kinase C (PKC) isoforms, in rat-1 fibroblasts expressing alpha(1A) adrenergic receptors. The aim of this study was to determine the contribution of atypical PKCzeta to PLD activation in response to PHE in these cells. Results: PHE stimulated a PLD activity as demonstrated by phosphatidylethanol production. PHE increased PKCzeta translocation to the particulate cell fraction in parallel with a time-dependent decrease in its activity. PKCzeta activity was reduced at 2 and 5 min and returned to a sub-basal level within 10-15 min. Ectopic expression of kinase-dead PKCzeta, but not constitutively active PKCzeta, potentiated PLD activation elicited by PHE. A cell-permeable pseudosubstrate inhibitor of PKCzeta reduced basal PKCzeta activity and abolished PHE-induced PLD activation. Conclusion: alpha(1A) adrenergic receptor stimulation promotes the activation of a PLD activity by a mechanism dependent on PKCzeta; Our data also suggest that catalytic activation of PKCzeta is not required for PLD stimulation.