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(Circulation Research. 2006;99:116.)
© 2006 American Heart Association, Inc.

Editorials

Nuclear Phospholipase D1 in Vascular Smooth Muscle

Specific Activation by G Protein–Coupled Receptors

Masuko Ushio-Fukai

From the Division of Cardiology, Department of Medicine, Emory University School of Medicine, Atlanta, Ga.

Correspondence to Masuko Ushio-Fukai, PhD, Division of Cardiology, Emory University School of Medicine, 101 Woodruff Circle, Rm. 319, Atlanta, GA 30322. Email mfukai@emory.edu

See related article, pages 132–139

Key Words: phospholipase D1 • nucleus • lysophosphatidic acid • angiotensin II • vascular smooth muscle

An extract of the first 250 words of the full text is provided, because this article has no abstract.

Activation of phospholipase D (PLD) is a major component of signal transduction cascades activated by G protein–coupled receptor (GPCR) agonists such as lysophosphatidic acid (LPA) and angiotensin II (Ang II), as well as growth factors such as PDGF and EGF that promote proliferation, migration, and inflammation of vascular smooth muscle cells (VSMCs). In mammalian cells, PLD catalyzes the hydrolysis of the principal membrane lipid phosphatidylcholine (PC), resulting in the formation of choline and bioactive lipid phosphatidic acid (PA). PA is subsequently metabolized to diacylglycerol by PA phosphohydrolase or to LPA by phospholipase A2. PLD been implicated in signal transduction, exocytosis and endocytosis, cell proliferation, cytoskeletal reorganization, and gene expression.^1–3 There are two mammalian PLD genes, PLD1 and PLD2, and two splice variants of each isoform. PLD1 has a low basal activity and is activated by the small GTP-binding proteins (Rho, Ral, and ADP ribosylation factor [Arf]) and protein kinase C (PKC). In contrast, PLD2 has a high basal activity and its in vitro activity is not or less responsive to PKC, Rho, or Arf.^1–3 Both PLD1 and PLD2 are activated by phosphatidylinositol 4,5-bisphosphate (PtdIns(4,5)P2), but PLD1 is inhibited whereas PLD2 is activated by oleic acid in vitro.^1,4 PLD1 and PLD2 have been proposed to mediate isoform-specific functions, based on their selective abilities and variable patterns of subcellular localization.² Numerous studies have used overexpression systems to show that PLD1 localizes to perinuclear vesicles,^5–7 plasma membrane,^8–10 including caveolin-enriched membrane,¹¹ and that PLD2 localizes to the plasma membrane,^5,12–14 and internalizes after . . . [Full Text of this Article]

Related Article:

Selective Activation of Nuclear Phospholipase D-1 by G Protein–Coupled Receptor Agonists in Vascular Smooth Muscle Cells

Stéphanie Gayral, Paul Déléris, Karine Laulagnier, Muriel Laffargue, Jean-Pierre Salles, Bertrand Perret, Michel Record, and Monique Breton-Douillon
Circ. Res. 2006 99: 132-139. [Abstract] [Full Text] [PDF]