Regulation of phospholipase D.
Structural studies of plant and bacterial members of the phospholipase D (PLD) superfamily are providing information about the role of the conserved HKD domains in the structure of the catalytic center and the catalytic mechanism of mammalian PLD isozymes (PLD1 and PLD2). Mutagenesis and sequence comparison studies have also defined the presence of pleckstrin homology and phox homology domains in the N-terminus and have demonstrated that a conserved sequence at the C-terminus is required for catalysis. The N- and C-terminal regions of PLD1 also contain interaction sites for protein kinase C, which can directly activate the enzyme through a non-phosphorylating mechanism. Small G proteins of the Rho and ADP-ribosylation factor families also directly regulate the enzyme, with RhoA binding to a sequence in the C-terminus. Certain tyrosine kinases and members of the Ras subfamily of small G proteins can activate the enzyme, but the mechanisms appear to be indirect. The mechanisms by which agonists activate PLD in vivo probably involve multiple pathways.
Exton
John H
JH
Howard Hughes Medical Institute and Vanderbilt University Medical Center, Nashville, TN 38232-0295, USA. john.exton@mcmail.vanderbilt.edu
D020727:ADP-Ribosylation Factors / Q000378:metabolism; D000818:Animals; D001665:Binding Sites; D002384:Catalysis; D019204:GTP-Binding Proteins / Q000378:metabolism; D015971:Gene Expression Regulation, Enzymologic; D006801:Humans; D010739:Phospholipase D / Q000378:metabolism* / Q000502:physiology*; D010766:Phosphorylation; D011485:Protein Binding; D011487:Protein Conformation; D020033:Protein Isoforms; D011493:Protein Kinase C / Q000378:metabolism; D017434:Protein Structure, Tertiary; D011505:Protein-Tyrosine Kinases / Q000378:metabolism; D014443:Tyrosine / Q000378:metabolism; D020742:rhoA GTP-Binding Protein / Q000378:metabolism
D020033:Protein Isoforms; D014443:Tyrosine; D011505:Protein-Tyrosine Kinases; D011493:Protein Kinase C; D010739:Phospholipase D; D019204:GTP-Binding Proteins; D020727:ADP-Ribosylation Factors; D020742:rhoA GTP-Binding Protein