Disease relevance of Pld2

• Recently, PLD2 was reported as a necessary intermediate in preventing apoptosis induced by hydrogen peroxide or hypoxia in rat pheochromocytoma (PC12) cells [1].
• Studies with pertussis toxin and other agents indicate that mastoparan stimulates PLD2 independently of G(i), ARF-1, protein kinase C, and calcium [2].
• The suppressive effect of Galpha(13)Q226L on rPLD2 was reversed by dominant negative N19RhoA and the C3 exoenzyme of Clostridium botulinum, further supporting a role for RhoA [3].
• The functional significance of PKCzeta and PLD2 in VSMC adhesion, spreading, and hypertrophy was investigated [4].
• These results demonstrate that ANG II-induced PLD activation is regulated by PKCzeta and suggest a crucial role of PKCzeta-dependent PLD2 in VSMC functions such as adhesion, spreading, and hypertrophy, which are associated with the pathogenesis of atherosclerosis and malignant hypertension [4].

High impact information on Pld2

• Moreover, overexpressed PLD1, but not PLD2, increases stimulated exocytosis in a phosphatidylinositol 4,5-bisphosphate-dependent manner, whereas catalytically inactive PLD1 inhibits it [5].
• Implication of phospholipase D2 in oxidant-induced phosphoinositide 3-kinase signaling via Pyk2 activation in PC12 cells [6].
• Essential role for phospholipase D2 activation downstream of ERK MAP kinase in nerve growth factor-stimulated neurite outgrowth from PC12 cells [7].
• Taken together, these results provide evidence that PLD2 functions as a downstream signaling effector of ERK in the NGF signaling pathway, which leads to neurite outgrowth by PC12 cells [7].
• Increased expression of wild type PLD2 (WT-PLD2) dramatically elongated neurites induced by NGF stimulation or transient expression of the active form of MAP kinase-ERK kinase (MEK-CA) [7].

Chemical compound and disease context of Pld2

• Since PA and DAG regulate Ca(2+) movements, we examined PLD2 and PAP2 in the sarcolemma (SL) and sarcoplasmic reticular (SR) membranes from hearts subjected to ischemia and reperfusion (I-R) [8].

Biological context of Pld2

• The Pld1 and Pld2 genes were localized to rat chromosome 2q23.3-->q24 proximal end and the proximal region of mouse Chromosome 3B, and rat chromosome 10q23.3-->q24 proximal end and mouse Chromosome 11B3, respectively [9].
• Overexpression of either PLD1 or PLD2 prevented the vascular smooth muscle cell apoptosis induced by serum withdrawal but not the calphostin-C-elicited apoptosis [10].
• Conversely, myogenesis was potentiated by PLD1b isoform overexpression but not by PLD2 overexpression, establishing that PLD1 is involved in this process [11].
• These results provide direct evidence for linkages between PLD2, ROS production, and S100B-RAGE-induced enhancement of Ang II-induced cell proliferation and activation of JAK2 in VSMCs [12].
• These data indicate that both PLD1 and PLD2 play a protective role against glutamate-induced cell death in PC12 cells [1].

Anatomical context of Pld2

• S100B-RAGE-mediated augmentation of angiotensin II-induced activation of JAK2 in vascular smooth muscle cells is dependent on PLD2 [12].
• These results suggest that BK activates PLD2 via PKCdelta in PC12 cells [13].
• PKCalpha and PKCdelta translocated from cytosol to membrane upon BK treatment, and rottlerin potently inhibited the activation of PLD2 by BK [13].
• Two mammalian phospholipase Ds (PLD1 and PLD2) have been cloned and both are present in RBL-2H3 mast cells [14].
• PLD1 is localised to secretory granules whilst PLD2 is localised to the plasma membrane, and the activity of both enzymes is increased upon antigen stimulation [14].

Associations of Pld2 with chemical compounds

• Bradykinin activates phospholipase D2 via protein kinase cdelta in PC12 cells [13].
• Treatment of the cultures with cycloheximide revealed that PLD1 and 2 proteins had biological half-lives of 2-3 days (PLD2) and 4-6 days (PLD1), respectively [15].
• Okadaic acid pretreatment overcame the decrease of ATP-induced thymidine incorporation by PLD2 overexpression [16].
• Taken together, we suggest that PLD2 activity might play a negative role in ATP-induced Fak and paxillin phosphorylation possibly through tyrosine phosphatases [17].
• Mastoparan selectively activates phospholipase D2 in cell membranes [2].

Other interactions of Pld2

• We conclude that both activation of ARF6 by antigen and a continual PLD2 activity are essential for local phosphatidylinositol(4,5)bisphosphate generation that regulates dynamic actin cytoskeletal rearrangements [18].
• To our knowledge, this study is the first demonstration that both ERK1/2 and p38 MAP kinase are involved in the PLD2 activation in PC12 cells exposed to H2O2 [19].
• Regulation of phospholipase D2 by GTP-dependent interaction with dynamin [20].
• ANG II-induced neointimal growth is mediated via cPLA2- and PLD2-activated Akt in balloon-injured rat carotid artery [21].
• Increased phospholipase D2 activity during hypoxia-induced death of PC12 cells: its possible anti-apoptotic role [22].

Analytical, diagnostic and therapeutic context of Pld2

• Chromosome locations of the Pld1a, Pld1b and Pld2 genes were determined in the rat and mouse by fluorescent in situ hybridization [9].
• Competitive RT-PCR analysis demonstrated a higher level of PLD1 mRNA than PLD2 mRNA (8.9 vs. 0.9amol/microg RNA, respectively) [15].
• We thus examined the developmental expression of PLD2 in postnatal brains by Northern blotting employing a non-radioactive RNA probe [23].
• We demonstrated the localization of the gene expression for PLD1 and PLD2 using in situ hybridization histochemistry in the brain of developing and mature rats [24].
• Western blot analysis showed that Akt phosphorylation that was increased by ANG II was inhibited in injured carotid arteries 2 days after exposure to cPLA2 or PLD2 siRNA or in injured arteries isolated after exposure to these agents for 30 min and then placed in tissue culture media for 24 h in the presence of these agents [21].

References