Disease relevance of Pld2

• Modulation of PLD2 activity by synucleins may play a role in some aspects of the pathophysiologies that characterize these neurodegenerative diseases [1].

High impact information on Pld2

• The effects of TPA on the down-regulation of basal or alpha-melanocyte-stimulating hormone-enhanced melanogenesis were almost completely blocked by expressing a lipase activity-negative mutant, LN-PLD2, but not by LN-PLD1 [2].
• Moreover, treatment with proteasome inhibitors completely blocked the PLD2-induced down-regulation of melanogenesis [2].
• Down-regulation of melanogenesis by phospholipase D2 through ubiquitin proteasome-mediated degradation of tyrosinase [2].
• Increases in cellular PA levels by direct PA application or overexpression of wild-type PLD2 mimicked the L1-dependent stimulation of neurite outgrowth [3].
• Activation of phospholipase D-2 by P2X(7) agonists in rat submandibular gland acini [4].

Biological context of Pld2

• This is much larger than the closely related mouse PLD2 (mPLD2) gene (17 kb) and indicates that a rapid 20-fold extension/contraction of the set of introns for one of the genes has occurred [5].
• Given that the two isoforms undertake unique molecular functions in cultured cells, our findings suggest that in vivo PLD1 and PLD2 may modulate neuronal plasticity via different pathways and cell types [6].
• Mammalian PLD activity derives from a family of membrane-associated enzymes that are activated by a wide variety of signal transduction events. cDNA species encoding human, mouse and rat PLD1 and PLD2 have recently been reported [7].
• Transient incorporation of PKC with mPLD2 and the phosphorylation of mPLD2 by a and b forms of PKC by UVC irradiation were observed [8].

Anatomical context of Pld2

• The L1-stimulated neurite outgrowth was inhibited by primary alcohols and by overexpression of lipase-deficient PLD2 [3].
• Using confocal microscopy, we demonstrate that the PLDs are expressed by different cell types in the mouse brain: PLD1 by neurons, and PLD2 by astrocytes [6].
• Using isoform-specific antibodies, PLD1 and PLD2 were found to be present predominantly in intracellular membranes, unlike the situation reported in other cells [9].
• Detailed analysis of the intracellular localisation of PLD1 and PLD2 revealed that these isoforms are differentially localised within adipocytes, implying functionally distinct roles for PLD activity in distinct subcellular compartments [9].
• Although LDs were induced in either PLD1- or PLD2-overexpressing CHO cells by oleic acid treatment, the stimulation of PLD activity was observed only in PLD1-CHO cells [10].

Associations of Pld2 with chemical compounds

• Two widely expressed mammalian phosphatidylcholine (PC)-specific phospholipases D (PLD), PLD1 and PLD2, have been identified [1].
• Retinoic acid (RA)-induced differentiation increased PLD1 and PLD2 mRNA levels and PLD activity that was responsive to phorbol myristate acetate [11].

Physical interactions of Pld2

• Recombinantly expressed PLD2 has high basal activity and is insensitive to GTP-binding protein activators of PLD1 [Colley, W. C., et al. (1997) Curr. Biol. 7, 191-201] [1].

Regulatory relationships of Pld2

• Using reverse transcription-polymerase chain reaction and Northern blotting techniques, we demonstrated that the PLD isoform stimulated by ATP was PLD-2 [4].

Other interactions of Pld2

• In the cerebellum of postnatal day 8 mice, PLD2 protein was abundantly expressed, while PLD1 expression was not detected [3].
• The level of PLD2 expression was increased by APP overexpression [12].
• Among the PLD isoforms, PLD2 expression was increased in all of the selected Fas-resistant clones [13].

Analytical, diagnostic and therapeutic context of Pld2

• The PLD2 isotype was detected by immunoprecipitation but PLD1 was not detected in M-1 cells [14].

References