Localization and possible functions of phospholipase D isozymes

Pulmonary phosphatidic acid phosphatase and lipid phosphate phosphohydrolase

“…Interest in this enzyme was prompted by the discovery that PLD activity, monitored as phosphatidylalcohol formation, was markedly increased by extracellular agonist-induced activation of cell surface G protein-coupled receptors and tyrosine kinase-linked receptors (10,60,62). Eukaryotic PLD appears to exist in two distinct forms: one group is stimulated by unsaturated free acids, whereas the other group is stimulated by polyphosphoinositides (60,61,139) The fatty acid-stimulated PLD activity has been purified from the lung as a 190-kDa membrane-intrinsic protein (183) but has not yet been cloned. Little is known about the regulation of this isoform, but it does not appear to be affected by small monomeric GTPases.…”

“…PLD1 isoforms have low basal activity and are inhibited by oleate. In the presence of PIP 2 or PIP 3 , PLD1a and PLD1b are activated by a number of small GTPases, including ADPribosylation factor (ARF) family members, Rho family members (RhoA, Rac, and Cdc42), Ral I and by PKCs, particularly PKC-␣ and PKC-␤ (61,69,81,96,113,139,140). Brefeldin A, a fungal metabolite that interferes with ARF GDP/GTP exchange, inhibits PLD1 activation and certain forms of vesicular trafficking (40,113).…”

“…Physiological functions for PLD are continuously being identified and include 1) activation of secretory processes, 2) nuclear envelope signaling during cell division, 3) differentiation, 4) superoxide formation, 5) immune responses, 6) vesicular transport, and 7) activation of the cytoskeletal system (40,113,139,140,213,228). Permeabilized cell preparations have proven useful for studies on endogenous and overexpressed PLD isoforms.…”

“…Permeabilized cell preparations have proven useful for studies on endogenous and overexpressed PLD isoforms. PLD1 has been implicated in Golgi, trans-Golgi, endosome/lysosome, and secretory vesicle membrane trafficking (40,113,139,140). PLD1 isoforms mRNA increase during differentiation of granulocytes, keratinocytes, and chondrocytes and during neonatal brain development.…”

“…In general, PLD1 localization is high in endosome/lysosome compartments, whereas PLD2 is more highly associated with the plasma membrane-and subplasma membrane-localized vesicles. However, PLD isoform functions can be cell specific, and these distinctions should not be considered absolute (40,113,139,140).…”