Expression and regulation of phospholipase D during neuronal differentiation of PC12 cells

Min, Do Sik; Ahn, Bong Hyun; Rhie, Duck-Joo; Yoon, San-Hyun; Hahn, Sang June; Kim, M.-S; Jo, Yang-Hyeok

doi:10.1016/s0028-3908(01)00070-3

Cited by 55 publications

(40 citation statements)

References 28 publications

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“…35,36 Moreover, PLD has been shown to be upregulated in TRKA-expressing rat pheochromocytoma (PC12) cells after NGF-stimulation. 37,38 Mammalian PLD activity is regulated by many factors including protein kinase C (PKC). 39 Accordingly, we observed elevated activation of PKC in DTrkA-induced leukemic cells (data not shown).…”

Section: Resultsmentioning

confidence: 99%

Remarkable leukemogenic potency and quality of a constitutively active neurotrophin receptor, ΔTrkA

et al. 2007

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Neurotrophins and their receptors play a key role in neurogenesis and survival. However, we and others have recently obtained evidence for a potential involvement of this receptor system in leukemia. To investigate mechanisms underlying the leukemogenic potential of activated neurotrophin receptor signaling, we analyzed in vivo leukemogenesis mediated by DTrkA, a mutant of TRKA (tropomyosin-related kinase A) isolated from a patient with acute myeloid leukemia (AML). Retroviral expression of DTrkA in myeloid 32D cells induced AML in syngeneic C3H/Hej mice (n ¼ 11/11, latency B4 weeks). C57Bl/6J mice transplanted with DTrkA-transduced primary lineage negative (Lin À ) bone marrow cells died of a transient polyclonal AML (n ¼ 7/15, latency of o12 days). Serial transplantation of AML cells did not re-induce this disease but rather acute lymphoblastic leukemia (ALL, latency 478 days). All primary recipients surviving the early AML developed clonal ALL or myeloid leukemia (latency 472 days) that required additional genetic lesions. PI3K and mTOR-raptor were identified as the crucial mediators of leukemic transformation, whereas STAT and MAP kinase signaling pathways were not activated. Thus, our findings reveal potent and unique transforming properties of altered neurotrophin receptor signaling in leukemogenesis, and encourage further analyses of neurotrophin receptors and downstream signaling events in hematological malignancies.

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Section: Resultsmentioning

confidence: 99%

Remarkable leukemogenic potency and quality of a constitutively active neurotrophin receptor, ΔTrkA

et al. 2007

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“…The antibodies used were as follows: anti-α-tubulin, anti-TCF-4, anti-NOS2, and anti-c-Myc (all from Santa Cruz Biotechnology); anti-β-catenin and anti-survivin (BD Biosciences); anti-phospho-GSK3β; anti-phospho-Akt; and anti-Akt (Cell Signaling Technology). A polyclonal anti-PLD antibody that recognizes both PLD1 and PLD2 was generated as previously described (29). Approval was obtained from the Institutional Review Board of The Catholic University of Korea, College of Medicine.…”

Section: Methodsmentioning

confidence: 99%

Phospholipase D1 Drives a Positive Feedback Loop to Reinforce the Wnt/β-Catenin/TCF Signaling Axis

et al. 2010

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Activation of the Wnt signaling pathway occurs frequently in human cancers, but an understanding of the targets and regulation of this important pathway remains incomplete. In this study, we report that phospholipase D (PLD), a cell survival mediator that is upregulated in cancer, is an important target of the Wnt signaling pathway that functions in a positive feedback loop to reinforce pathway output. PLD1 expression and activity was enhanced by treatment with Wnt3a and glycogen synthase kinase-3 inhibitors, and the Wnt pathway-regulated transcription factors β-catenin and TCF-4 were required for this effect. Three functional TCF-4-binding sites were identified within the PLD1 promoter. Interestingly, suppressing PLD1 blocked the ability of β-catenin to transcriptionally activate PLD1 and other Wnt target genes by preventing β-catenin/ TCF-4 complex formation. Conversely, tactics to elevate intracellular levels of phosphatidic acid, the product of PLD1 enzyme activity, enhanced β-catenin/TCF-4 complex formation as well as β-catenin-dependent TCF transcriptional activity. In cell-based assays, PLD1 was necessary for the anchorage-independent growth driven by Wnt/β-catenin signaling, whereas β-catenin/TCF-4 was necessary for the anchorage-independent growth driven by PLD1 activation. Taken together, our findings define a function for PLD1 in a positive feedback loop of Wnt/β-catenin/TCF-4 signaling that provides new mechanistic insights into cancer, with implications of novel strategies to disrupt Wnt signaling in cancer. Cancer Res; 70(10); 4233-42. ©2010 AACR.

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“…Rabbit polyclonal antibodies against phospho-Akt and Akt were obtained from Cell Signaling Technology (Boston, MA). Polyclonal antibody that recognizes both PLD1 and PLD2 was generated as previously described (19).…”

Section: Methodsmentioning

confidence: 99%

Phospholipase D Prevents Etoposide-Induced Apoptosis by Inhibiting the Expression of Early Growth Response-1 and Phosphatase and Tensin Homologue Deleted on Chromosome 10

et al. 2006

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Phospholipase D (PLD) has emerged as a critical regulator of cell proliferation and survival signaling. We show for the first time that elevated expression of PLD isozymes attenuates expression of the tumor suppressors early growth response-1 (Egr-1) and the phosphatase and tensin homologue deleted on chromosome 10 (PTEN) tumor suppressor and apoptosis during etoposide treatment. When formation of phosphatidic acid was inhibited by overexpression of catalytically inactive PLD during etoposide treatment, expression of Egr-1 and PTEN and the apoptotic effect of etoposide were not inhibited. This suggests that PLD inhibits expression of these tumor suppressors and inhibits apoptosis. Deletion of a specific Egr-1-binding site present in the PTEN promoter blocked etoposide-induced PTEN activity and elevated expression of PLD decreased the sensitivity to apoptosis induced by ectopic expression of Egr-1. Etoposide-induced activation of Akt was potentiated by overexpression of PLD and PLD-stimulated suppression of Egr-1 was blocked by inhibition of phosphatidylinositol 3-kinase/Akt survival pathway at the both transcriptional and posttranscriptional levels. These results show that survival signals generated by PLD attenuate expression of Egr-1 by activation of phosphatidylinositol 3-kinase signaling pathway and induction of PTEN by Egr-1, which confers resistance to apoptosis. (Cancer Res 2006; 66(2): 784-93)

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Expression and regulation of phospholipase D during neuronal differentiation of PC12 cells

Cited by 55 publications

References 28 publications

Remarkable leukemogenic potency and quality of a constitutively active neurotrophin receptor, ΔTrkA

Remarkable leukemogenic potency and quality of a constitutively active neurotrophin receptor, ΔTrkA

Phospholipase D1 Drives a Positive Feedback Loop to Reinforce the Wnt/β-Catenin/TCF Signaling Axis

Phospholipase D Prevents Etoposide-Induced Apoptosis by Inhibiting the Expression of Early Growth Response-1 and Phosphatase and Tensin Homologue Deleted on Chromosome 10

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