Regulation of phospholipase D by phosphorylation-dependent mechanisms.
The rapid production of phosphatidic acid following receptor stimulation has been demonstrated in a wide range of mammalian cells. Virtually every cell uses phosphatidylcholine as substrate to produce phosphatidic acid in a controlled reaction catalyzed by specific PLD isoforms. Considerable effort has been directed at studying the regulation of PLD activities and subsequent work has characterized a family of proteins including PLD1 and PLD2. Whereas both PLD enzymes are dependent on phosphatidylinositol 4, 5-bisphosphate for activity only the PLD1 isoform was strongly stimulated by the small GTPases ARF and RhoA and by protein kinase Calpha as well. A role for tyrosine kinase activities in the membrane recruitment of small GTPases, in the synthesis of phosphatidylinositol 4,5-bisphosphate and tyrosine phosphorylation of PLD1 and PLD2 has been uncovered. However, it still not clear exactly how tyrosine phosphorylation of proteins contributes to PLD activation in cells. Here we review the data linking tyrosine phosphorylation of proteins to the activation of PLD and describe recent finding on the sites and possible mechanisms of action of tyrosine kinases in receptor-mediated PLD activation. Finally, a model illustrating the potential complex interplay linking these signaling events with the activation of PLD is presented.
Houle
M G
MG
Centre de Recherche en Rhumatologie et Immunologie, Centre de Recherche du CHUQ, Pavillon CHUL, Faculty of Medicine, Université Laval, Ste-Foy, Quebec, Canada.
Bourgoin
S
S
D000818:Animals; D004789:Enzyme Activation; D006801:Humans; D019269:Phosphatidylinositol 4,5-Diphosphate / Q000494:pharmacology; D010739:Phospholipase D / Q000737:chemistry / Q000378:metabolism*; D010766:Phosphorylation; D011493:Protein Kinase C / Q000494:pharmacology; D011505:Protein-Tyrosine Kinases / Q000494:pharmacology
D019269:Phosphatidylinositol 4,5-Diphosphate; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; C105606:phospholipase D2; D010739:Phospholipase D; C106801:phospholipase D1