Phospholipase D2, a distinct phospholipase D isoform with novel regulatory properties that provokes cytoskeletal reorganization

Colley, William C.; Sung, Tsung-Chang; Roll, Richard; Jenco, John M.; Hammond, Scott M.; Altshuller, Yelena M.; Bar–Sagi, Dafna; Morris, Andrew J.; Frohman, Michael A.

doi:10.1016/s0960-9822(97)70090-3

Cited by 672 publications

(759 citation statements)

References 50 publications

(82 reference statements)

Supporting

Mentioning

690

Contrasting

Unclassified

Order By: Relevance

“…Overexpressed PLD2 has been demonstrated in the plasma membrane as well as intracellular vesicles and the nucleus (18,64,67). Like PLD1, PLD2 has been demonstrated to undergo agonist-induced translocation between membrane compartments (25,67,71,72).…”

Section: Discussionmentioning

confidence: 99%

“…This ubiquitous enzyme family is found in viruses, bacteria, fungi, plants, and mammals, and is characterized by a conserved motif, HXKX 4 DX 6 G(G/S), which encompasses the catalytic HKD triad (21)(22)(23). Two mammalian PLDs have been identified and each exhibits complex regulation in vivo and in vitro (18,19,24,25). PLD1 is activated by GTPases of the Rho, Ral, and ADP ribosylation factor families, as well as by protein kinase C (PKC); and phosphatidylinositol-4,5-bisphosphate (PI(4,5)P 2 ) serves as an essential cofactor (24).…”

mentioning

confidence: 99%

“…PLD1 is activated by GTPases of the Rho, Ral, and ADP ribosylation factor families, as well as by protein kinase C (PKC); and phosphatidylinositol-4,5-bisphosphate (PI(4,5)P 2 ) serves as an essential cofactor (24). PLD2 also requires PI(4,5)P 2 , but in contrast to PLD1, exhibits relatively high in vitro activity in the absence of protein cofactors, and appears to be primarily subject to negative regulation (25). However, recent data support a role for both ADP ribosylation factor GTPases and PKC in stimulated activation of PLD2 (26,27).…”

mentioning

confidence: 99%

See 2 more Smart Citations

Phospholipases D1 and D2 Coordinately Regulate Macrophage Phagocytosis

Barton¹,

Bourgoin²,

Kusner

2004

The Journal of Immunology

View full text Add to dashboard Cite

Phagocytosis is a fundamental feature of the innate immune system, required for antimicrobial defense, resolution of inflammation, and tissue remodeling. Furthermore, phagocytosis is coupled to a diverse range of cytotoxic effector mechanisms, including the respiratory burst, secretion of inflammatory mediators and Ag presentation. Phospholipase D (PLD) has been linked to the regulation of phagocytosis and subsequent effector responses, but the identity of the PLD isoform(s) involved and the molecular mechanisms of activation are unknown. We used primary human macrophages and human THP-1 promonocytes to characterize the role of PLD in phagocytosis. Macrophages, THP-1 cells, and other human myelomonocytic cells expressed both PLD1 and PLD2 proteins. Phagocytosis of complement-opsonized zymosan was associated with stimulation of the activity of both PLD1 and PLD2, as demonstrated by a novel immunoprecipitation-in vitro PLD assay. Transfection of dominant-negative PLD1 or PLD2 each inhibited the extent of phagocytosis (by 55–65%), and their combined effects were additive (reduction of 91%). PLD1 and PLD2 exhibited distinct localizations in resting macrophages and those undergoing phagocytosis, and only PLD1 localized to the phagosome membrane. The COS-7 monkey fibroblast cell line, which has been used as a heterologous system for the analysis of receptor-mediated phagocytosis, expressed PLD2 but not PLD1. These data support a model in which macrophage phagocytosis is coordinately regulated by both PLD1 and PLD2, with isoform-specific localization. Human myelomonocytic cell lines accurately model PLD-dependent signal transduction events required for phagocytosis, but the heterologous COS cell system does not.

show abstract

Section: Discussionmentioning

confidence: 99%

mentioning

confidence: 99%

mentioning

confidence: 99%

See 1 more Smart Citation

Phospholipases D1 and D2 Coordinately Regulate Macrophage Phagocytosis

Barton¹,

Bourgoin²,

Kusner

2004

The Journal of Immunology

View full text Add to dashboard Cite

show abstract

“…Recent advances in the molecular understanding of PLD have brought new insights into the control and cellular roles of PLD. An intracellular PLD was first cloned from castor bean (3), and the cloning of PLDs has since been reported from Arabidopsis (4,5), rice, maize (6), yeast (7), human (8), and mouse (9). Analysis of the PLD sequences has led to the identification of probable catalytic and regulatory domains of PLD (10,11).…”

mentioning

confidence: 99%

“…The polyphosphoinositide activation of plant PLDs is a property shared by PLDs cloned from mammals and yeast (8,9,13). This property has been proposed to be physiologically important because, in addition to being precursors for signaling messengers, polyphosphoinositides themselves can also modulate the functions of proteins through direct binding.…”

mentioning

confidence: 99%

Molecular Heterogeneity of Phospholipase D (PLD)

Khatiwada¹,

Pappan²,

Wang

1997

Journal of Biological Chemistry

153

View full text Add to dashboard Cite

Changes in phospholipase D isoform activity and expression in multidrug-resistant human cancer cells

et al. 2000

View full text Add to dashboard Cite

Multidrug resistance (MDR) is a major cause of failure of cancer chemotherapy and is often associated with elevated expression of drug transporters such as P-glycoprotein (P-gp) in the cancer cells. MDR is, however, accompanied by additional biochemical changes including modifications of membrane composition and properties. We have shown that MDR is associated with a massive up-regulation of caveolin expression and an elevated surface density of caveolae. We report that phospholipase D (PLD), a constituent enzyme of caveolae and detergent-insoluble glycolipid-rich membranes (DIGs), is up-regulated in human MDR cancer cells. Lysates of HT-29-MDR human colon adenocarcinoma cells, MCF-7 AdrR human breast adenocarcinoma cells and the corresponding parental drug-sensitive cells, were fractionated on discontinuous sucrose density gradients. PLD activity was found to be enriched in low density fractions that contain DIGs and caveolar membranes, and the activity in these fractions was 4-to 6-fold higher in the MDR cells compared with the parental drug-sensitive cells. Utilizing specific antibodies to PLD1 and PLD2, the distribution of PLD isoforms along the gradient was determined and the PLD localized in DIGs and caveolar membranes has been identified as PLD2. Northern blot analysis of PLD1 and PLD2 mRNA levels has indicated that PLD2 mRNA is elevated in both HT-29-MDR and MCF-7 AdrR cells. PLD1 mRNA levels were either unchanged or reduced in the MDR cells. Finally, in vivo experiments have confirmed previous results showing that activation of PLD by phorbol esters is markedly potentiated in the MDR cells. We conclude that MDR is accompanied by an increase in PLD2 activity in DIGs and caveolar membranes.

show abstract

Phospholipase D2, a distinct phospholipase D isoform with novel regulatory properties that provokes cytoskeletal reorganization

Abstract: PLD2 is a newly identified mammalian PLD isoform with novel regulatory properties. Our findings suggest that regulated secretion and morphological reorganization, the two most frequently proposed biological roles for PLD, are likely to be effected separately by PLD1 and PLD2.

Cited by 672 publications

References 50 publications

Phospholipases D1 and D2 Coordinately Regulate Macrophage Phagocytosis

Phospholipases D1 and D2 Coordinately Regulate Macrophage Phagocytosis

Molecular Heterogeneity of Phospholipase D (PLD)

Changes in phospholipase D isoform activity and expression in multidrug-resistant human cancer cells

Contact Info

Product

Resources

About