title: Biochemistry and cell biology of phospholipase D in human neutrophils.
abstract: Neutrophils play a major role host defense against invading microbes. Recent studies have emphasized the importance of the phospholipase D (PLD) in the signalling cascade leading to neutrophil activation. Phospholipase D catalyzes the hydrolysis of phospholipids to generate phosphatidic acid with secondarily generation of diradylglycerol; both of these products have been implicated as second messengers. Herein, we discuss the regulation and the biochemistry of the receptor-regulated PLD in human neutrophils. In vivo and in vitro studies suggest an activation mode in which initial receptor-linked activation of phospholipase C generates diacylglycerol and inositol trisphosphate. The resulting calcium flux along with the diacylglycerol activate a conventional isoform of protein kinase C (PKC), probably PKC beta 1. This PKC, in turn phosphorylates a plasma membrane component resulting in PLD activation and a second outpouring of diradylglycerol. The small GTP-binding proteins, RhoA and ARF, also participate in this process, and synergize with a 50 kDa cytosolic regulatory factor.
authors.affiliation: Department of Biochemistry and Molecular Biology, New York Medical College, Valhalla 10595, USA.
authors.forename: S C
authors.initials: SC
authors.lastname: Olson
authors.forename: J D
authors.initials: JD
authors.lastname: Lambeth
mesh_terms: D000818:Animals; D006801:Humans; D009504:Neutrophils / Q000201:enzymology*; D010739:Phospholipase D / Q000097:blood / Q000378:metabolism / Q000502:physiology*
chemical_list: D010739:Phospholipase D