Protein kinase Cζ regulates phospholipase D activity in rat-1 fibroblasts expressing the α1A adrenergic receptor
1 Department of Pharmacology and Center for Connective Tissue Diseases and Vascular Biology, College of Medicine, The University of Tennessee Health Science Center, 874 Union Avenue, Memphis, TN 38163, USA
2 Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHUQ, Universite Laval, Sainte-Foy, QC, Canada
BMC Cell Biology 2004, 5:4 doi:10.1186/1471-2121-5-4Published: 21 January 2004
Phenylephrine (PHE), an α1 adrenergic receptor agonist, increases phospholipase D (PLD) activity, independent of classical and novel protein kinase C (PKC) isoforms, in rat-1 fibroblasts expressing α1A adrenergic receptors. The aim of this study was to determine the contribution of atypical PKCζ to PLD activation in response to PHE in these cells.
PHE stimulated a PLD activity as demonstrated by phosphatidylethanol production. PHE increased PKCζ translocation to the particulate cell fraction in parallel with a time-dependent decrease in its activity. PKCζ activity was reduced at 2 and 5 min and returned to a sub-basal level within 10–15 min. Ectopic expression of kinase-dead PKCζ, but not constitutively active PKCζ, potentiated PLD activation elicited by PHE. A cell-permeable pseudosubstrate inhibitor of PKCζ reduced basal PKCζ activity and abolished PHE-induced PLD activation.
α1A adrenergic receptor stimulation promotes the activation of a PLD activity by a mechanism dependent on PKCζ; Our data also suggest that catalytic activation of PKCζ is not required for PLD stimulation.