title: Regulation of phospholipase D.
abstract: Phospholipase D (PLD) is a widely distributed enzyme that is under elaborate control by hormones, neurotransmitters, growth factors and cytokines in mammalian cells. Protein kinase C (PKC) plays a major role in the regulation of the PLD1 isozyme through interaction with its N-terminus. PKC activates this isozyme by a non-phosphorylation mechanism in vitro, but phosphorylation plays a role in the action of PKC on the enzyme in vivo. Although PLD1 can be phosphorylated by PKC in vitro, it is unclear that this occurs in vivo. Small GTPases of the ADP-ribosylation factor (ARF) and Rho families directly activate PLD1 in vitro and there is evidence that Rho proteins are involved in agonist regulation of PLD1 in vivo. ARF proteins stimulate PLD activity in the Golgi apparatus, but the role of these proteins in agonist regulation of the enzyme is less clear. PLD1 undergoes tyrosine phosphorylation in response to H(2)O(2) treatment of cells. The functional consequence of this phosphorylation and soluble tyrosine kinase(s) involved are presently unknown.
authors.affiliation: Howard Hughes Medical Institute and Department of Molecular Physiology and Biophysics Vanderbilt University School of Medicine, Nashville, TN 37232-0295, USA. john.exton@mcmail.vanderbuilt.edu
authors.forename: J H
authors.initials: JH
authors.lastname: Exton
mesh_terms: D020727:ADP-Ribosylation Factors; D000818:Animals; D002118:Calcium / Q000502:physiology; D002460:Cell Line; D002518:Ceramides / Q000378:metabolism; D004789:Enzyme Activation; D020558:GTP Phosphohydrolases / Q000502:physiology; D019204:GTP-Binding Proteins / Q000502:physiology; D006801:Humans; D008565:Membrane Proteins; D010716:Phosphatidylinositols / Q000378:metabolism; D010739:Phospholipase D / Q000378:metabolism*; D011493:Protein Kinase C / Q000502:physiology; D011505:Protein-Tyrosine Kinases / Q000502:physiology
chemical_list: D002518:Ceramides; D008565:Membrane Proteins; D010716:Phosphatidylinositols; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D010739:Phospholipase D; C106801:phospholipase D1; C097313:ADP-ribosylation factor related proteins; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D020727:ADP-Ribosylation Factors; D002118:Calcium