Regulation of Phospholipase D by Protein Kinase C Is Synergistic with ADP-ribosylation Factor and Independent of Protein Kinase Activity (*)

Phospholipase D (PLD) which was partially purified from membranes of porcine brain could be stimulated by multiple cytosolic components; these included ADP-ribosylation factor (Arf) and RhoA, which required guanine nucleotides for activity, and an unidentified factor which activated the enzyme in a nucleotide-independent manner (Singer, W. D., Brown, H. A., Bokoch, G. M., and Sternweis, P. C.(1995) J. Biol. Chem. 270, 14944-14950). Here, we report purification of the latter factor, its identification as the α isoform of protein kinase C (PKCα), and characterization of its regulation of PLD activity. Stimulation of PLD by purified PKCα or recombinant PKCα (rPKCα) occurred in the absence of any nucleotide and required activators such as Ca or phorbol ester. This action was synergistic with stimulation of PLD evoked by either Arf or RhoA. Dephosphorylation of rPKCα with protein phosphatase 1 or 2A resulted in a loss of its kinase activity, but had little effect on its ability to stimulate PLD either alone or in conjunction with Arf. Staurosporine inhibited the kinase activity of PKCα without affecting activation of PLD. Finally, gel filtration of PKCα that had been cleaved with trypsin demonstrated that stimulatory activity for PLD coeluted with the regulatory domain of the enzyme. These data indicate that PKC may regulate signaling events through direct molecular interaction with downstream effectors as well as through its well characterized catalytic modification of proteins by phosphorylation.

• Publication year

  1996

• Venue

  Journal of Biological Chemistry

• Publication date

  1996-02-23

• Fields of study

  Biology, Medicine, Chemistry

• Identifiers
  DOI 10.1074/JBC.271.8.4504PMID 8626805
• External record

  Open on Semantic Scholar

• Source metadata

  Semantic Scholar, PubMed

• No claims are published for this paper.

• No concepts are published for this paper.

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