Disease relevance of Pld1

• Treatment of B16 mouse melanoma cells with 12-O-tetradecanoylphorbol-13-acetate (TPA) resulted in the activation of PLD and a decrease in melanin content [1].
• Here, we investigated the expression of PLD during differentiation of pluripotent embryonal carcinoma cells (P19) into astrocytes and neurons [2].
• Involvement of phospholipase D1 in melanogenesis of mouse B16 melanoma cells [3].
• We found that Streptomyces sp. PLD was much less potent at inhibiting proliferation than S. chromofuscus PLD, with a half-maximal inhibitory concentration of 0.05 versus less than 0.001 IU per ml for S. chromofuscus PLD [4].
• A20 murine lymphoma cells undergoing Fas-mediated apoptosis showed increase in the activity of phospholipase D (PLD), which is involved in proliferative or mitogenic cellular responses [5].

Psychiatry related information on Pld1

• The subcellular localization of PLD1 is altered, and PLD enzymatic activity is reduced in cells expressing familial Alzheimer's disease (FAD) PS1 mutations compared with PS1wt cells [6].

High impact information on Pld1

• An early response to the tyrosine kinase activity of v-Src is an increase in phospholipase D (PLD) activity, which leads to the generation of biologically active lipid second messengers, including phosphatidic acid, lysophosphatidic acid and diacylglycerol [7].
• Thus RalA is involved in the tyrosine kinase activation of PLD through its unique N terminus, and that PLD is a downstream target of a Ras/Ral GTPase cascade [7].
• However, there was no PLD activation nor chlamydial killing in ATP-treated P2X(7)R-deficient macrophages [8].
• P2X(7)R stimulation also resulted in macrophage death, but fusion with lysosomes preceded macrophage death and PLD inhibition did not prevent macrophage death [8].
• Overexpression of PLD1 in PS1wt cells promotes generation of betaAPP-containing vesicles from the trans-Golgi network [6].

Chemical compound and disease context of Pld1

• On the contrary, pertussis toxin-sensitive GTP-binding protein and extracellular Ca2+ might play important roles in the pathway of PGE2-induced PLD activation [9].
• PGE2-induced PLD activity was markedly suppressed by either chelating extracellular Ca2+ by EGTA or pertussis toxin [9].
• The stimulation of the PLD pathway by oxidized LDL may be of importance in atherogenesis, because PLD activation leads to generation of important second messengers such as phosphatidate, lysophosphatidate, and diacylglycerol, which are known to regulate many cellular functions [10].
• PLD1 in mitochondrial membranes from scrapie brains, but not from control brains, was tyrosine phosphorylated [11].
• PLD activation leads to the generation of important second messengers such as phosphatidic acid, lysophosphatidic acid, and diacylglycerol, all of which can regulate cellular responses involved in atherogenesis and inflammation [12].

Biological context of Pld1

• 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 [1].
• Phospholipase D (PLD) catalyzes the hydrolysis of phosphatidylcholine to generate phosphatidic acid and choline [13].
• Mouse PLD1 (mPLD1) contains 28 exons and spans approximately 147 kb [13].
• These findings place PLD as an important component in PDGF-BB- and PMA-stimulated intracellular signalling leading to gene activation in Cl8 cells, while EGF does not require PLD [14].
• 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 [15].

Anatomical context of Pld1

• The impaired neurite outgrowth capacity in FAD mutant neurons was corrected by introducing PLD1 into these cells [6].
• Participation of phospholipase D and alpha/beta-protein kinase C in growth factor-induced signalling in C3H10T1/2 fibroblasts [14].
• Our results suggest a role for PLD expression/activity during keratinocyte differentiation [16].
• 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 [15].
• Increased expression of two phospholipase D isoforms during experimentally induced hippocampal mossy fiber outgrowth [15].

Associations of Pld1 with chemical compounds

• Conversely, inhibition of PLD1 activity by 1-butanol decreases betaAPP trafficking in both wt and PS1-deficient cells [6].
• 1-Butanol, but not 2-butanol, completely blocked the TPA-induced inhibition of melanogenesis, suggesting the involvement of PLD in this event [1].
• Because primary alcohols suppress the formation of the signaling lipid phosphatidic acid (PA) by phospholipase D (PLD), this observation prompted us to investigate whether PLD plays a role in the L1-mediated neurite outgrowth in CGNs [17].
• Neuronal differentiation of the P19 cells by retinoic acid did not affect the basal or PMA stimulated-PLD activity [18].
• Two widely expressed mammalian phosphatidylcholine (PC)-specific phospholipases D (PLD), PLD1 and PLD2, have been identified [19].

Physical interactions of Pld1

• 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] [19].
• Investigating possible mitogenic signaling pathways we show for the first time that prolactin is coupled to a sustained phospholipase D (PLD) activation, with an efficacy similar to the phorbol ester and astrocytic mitogen 12-tetradecanoylphorbol-13-acetate (TPA) [20].

Regulatory relationships of Pld1

• PLD1 activity in the LD-enriched fractions was stimulated by exogenously added Arf1 [21].
• Using reverse transcription-polymerase chain reaction and Northern blotting techniques, we demonstrated that the PLD isoform stimulated by ATP was PLD-2 [22].
• Here, we have demonstrated that inhibiting PLD signal generation with 1-butanol reduced TPA-stimulated transglutaminase activity, a marker of keratinocyte differentiation [23].
• Thus, choline, which enters the cells through the BzATP-induced pores, can act to inhibit P2z receptor-stimulated PLD activity but not pore formation [24].
• Insulin-stimulated plasma membrane fusion of Glut4 glucose transporter-containing vesicles is regulated by phospholipase D1 [25].

Other interactions of Pld1

• Surface delivery of betaAPP is also increased by PLD1 in these cells [6].
• Taken together, the data suggest that the activation of Arf1-dependent PLD1 occurs in LDs and may be involved in their physiological function [21].
• Furthermore, co-existence of PLD1, Arf1, and ADRP was observed in the LD-enriched subcellular fractions obtained from oleic acid-treated NIH3T3 cells by Western blot analysis [21].
• Since TPA activates all conventional and novel PKC isoforms directly, yet cannot overcome 1-butanol-mediated inhibition, this result suggests that PLD mediates its effects on transglutaminase activity (and keratinocyte differentiation) through an effector enzyme system distinct from the conventional or novel PKC isoenzymes [23].
• Retinoic acid-induced differentiation into astrocytes and glutamatergic neurons is associated with expression of functional and activable phospholipase D [2].

Analytical, diagnostic and therapeutic context of Pld1

• In situ hybridization studies demonstrated that the highest levels of PLD-1 expression are in the more differentiated (spinous and granular) layers of the epidermis, with little expression in basal keratinocytes [16].
• The PLD2 isotype was detected by immunoprecipitation but PLD1 was not detected in M-1 cells [26].
• These results suggest that P2X(7)R ligation leads to PLD activation, which is directly responsible for inhibition of infection [8].
• Using RT-PCR, 3T3-L1 adipocytes were found to express two isoforms of phospholipase D, specifically PLD1b and PLD2a [27].
• Furthermore, microinjection of purified PLD into cultured adipocytes markedly potentiated the effect of a submaximal concentration of insulin to stimulate GLUT4 translocation to cell surface membranes [28].

References