ArticleMolecular and cellular biology2003
Elevated phospholipase D activity in H-Ras- but not K-Ras-transformed cells by the synergistic action of RalA and ARF6.
Article in Molecular and cellular biology, 2003. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 27 papers.
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Who cites it
27 citing papers in PubMed, 54 citations in OpenAlex.
- Phospholipase D2 downregulates interleukin-1β secretion from tumor-associated macrophages to suppress bladder cancer progression.Cancer science · 2025Article
- Phosphatidylcholine-Derived Lipid Mediators: The Crosstalk Between Cancer Cells and Immune Cells.Frontiers in immunology · 2022Review
- ADP-ribosylation factor 6 expression increase in oesophageal adenocarcinoma suggests a potential biomarker role for it.PloS one · 2022Article
- Tumor cell-secreted PLD increases tumor stemness by senescence-mediated communication with microenvironment.Oncogene · 2019Article
- The Small GTPase Ral orchestrates MVB biogenesis and exosome secretion.Small GTPases · 2018Article
- Ral-Arf6 crosstalk regulates Ral dependent exocyst trafficking and anchorage independent growth signalling.Cellular signalling · 2016Article
- ADP-Ribosylation Factor 1 Regulates Proliferation, Migration, and Fusion in Early Stage of Osteoclast Differentiation.International journal of molecular sciences · 2015Article
- PLD3 in Alzheimer's disease.Molecular neurobiology · 2015Review
- Phospholipase D in cell signaling: from a myriad of cell functions to cancer growth and metastasis.The Journal of biological chemistry · 2014Review
- Regulation of TOR by small GTPases.EMBO reports · 2012Review
- Phospholipase D mediates nutrient input to mammalian target of rapamycin complex 1 (mTORC1).The Journal of biological chemistry · 2011Article
- The RalGEF-Ral Effector Signaling Network: The Road Less Traveled for Anti-Ras Drug Discovery.Genes & cancer · 2011Article
- Heterogeneity of phosphatidic acid levels and distribution at the plasma membrane in living cells as visualized by a Föster resonance energy transfer (FRET) biosensor.The Journal of biological chemistry · 2010Article
- Mutated ras induced PLD1 gene expression through increased Sp1 transcription factor.Nagoya journal of medical science · 2009Article
- Phosphatidic acid signaling to mTOR: signals for the survival of human cancer cells.Biochimica et biophysica acta · 2009Review
- Distinct roles of RalA and RalB in the progression of cytokinesis are supported by distinct RalGEFs.The EMBO journal · 2008Article
- Honokiol suppresses survival signals mediated by Ras-dependent phospholipase D activity in human cancer cells.Clinical cancer research : an official journal of the American Association for Cancer Research · 2008Article
- Podosomes and Invadopodia: Related structures with Common Protein Components that May Promote Breast Cancer Cellular Invasion.Breast cancer : basic and clinical research · 2008Article
- Phospholipase D provides a survival signal in human cancer cells with activated H-Ras or K-Ras.Cancer letters · 2007Article
- Phospholipase D signaling: orchestration by PIP2 and small GTPases.Naunyn-Schmiedeberg's archives of pharmacology · 2007Review
Corrections and comments
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Authors and funding
7 authors at 2 institutions in 1 country.
Funding
Abstract
Phospholipase D (PLD) activity is elevated in response to the oncogenic stimulus of H-Ras but not K-Ras. H-Ras and K-Ras have been reported to localize to different membrane microdomains, with H-Ras localizing to caveolin-enriched light membrane fractions. We reported previously that PLD activity elevated in response to mitogenic stimulation is restricted to the caveolin-enriched light membrane fractions. PLD activity in H-Ras-transformed cells is dependent upon RalA, and consistent with a lack of elevated PLD activity in K-Ras-transformed cells, RalA was not activated in K-Ras-transformed cells. Although H-Ras-induced PLD activity is dependent upon RalA, an activated mutant of RalA is not sufficient to elevate PLD activity. We reported previously that RalA interacts with PLD activating ADP ribosylation factor (ARF) proteins. In cells transformed by H-Ras, we found increased coprecipitation of ARF6 with RalA. Moreover, ARF6 colocalized with RalA in light membrane fractions. Interestingly, ARF6 protein levels were elevated in H-Ras- but not K-Ras-transformed cells. A dominant-negative mutant of ARF6 inhibited PLD activity in H-Ras-transformed NIH 3T3 cells. Activated mutants of either ARF6 or RalA were not sufficient to elevate PLD activity in NIH 3T3 cells; however, expression of both activated RalA and activated ARF6 in NIH 3T3 cells led to increased PLD activity. These data suggest a model whereby H-Ras stimulates the activation of both RalA and ARF6, which together lead to the elevation of PLD activity.
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Registered trials
Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the OpenQuestion graph.