ArticleCellular signalling2013
Increased cell growth due to a new lipase-GEF (Phospholipase D2) fastly acting on Ras.
Article in Cellular signalling, 2013. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 14 papers.
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Who cites it
14 citing papers in PubMed, 19 citations in OpenAlex.
- Upregulated phospholipase D2 expression and activity is related to the metastatic properties of melanoma.Oncology letters · 2022Article
- 40 Years of RAS-A Historic Overview.Genes · 2021Review
- Ras GEF Mouse Models for the Analysis of Ras Biology and Signaling.Methods in molecular biology (Clifton, N.J.) · 2021Article
- Mammalian phospholipase D: Function, and therapeutics.Progress in lipid research · 2020Review
- Phospholipase D2 in prostate cancer: protein expression changes with Gleason score.British journal of cancer · 2019Article
- Mechanism of enzymatic reaction and protein-protein interactions of PLD from a 3D structural model.Cellular signalling · 2015Article
- A river runs through it: how autophagy, senescence, and phagocytosis could be linked to phospholipase D by Wnt signaling.Journal of leukocyte biology · 2014Review
- Phospholipase D signaling pathways and phosphatidic acid as therapeutic targets in cancer.Pharmacological reviews · 2014Review
- Cellular and physiological roles for phospholipase D1 in cancer.The Journal of biological chemistry · 2014Review
- Functional regulation of phospholipase D expression in cancer and inflammation.The Journal of biological chemistry · 2014Review
- Phospholipase D in cell signaling: from a myriad of cell functions to cancer growth and metastasis.The Journal of biological chemistry · 2014Review
- Phosphatidic acid, phospholipase D and tumorigenesis.Advances in biological regulation · 2014Article
- Phospholipase D (PLD) drives cell invasion, tumor growth and metastasis in a human breast cancer xenograph model.Oncogene · 2013Article
- A GEF-to-phospholipase molecular switch caused by phosphatidic acid, Rac and JAK tyrosine kinase that explains leukocyte cell migration.Journal of cell science · 2013Article
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Authors and funding
3 authors at 1 institution in 1 country.
Funding
Abstract
We report the novel finding that Phospholipase D2 (PLD2), through its PX and PH domains, binds specifically to Ras and catalyzes the GDP/GTP exchange (i.e., is a GEF), with potency comparable to Ras-GRF-1, a known Ras-GEF. Cells overexpressing PLD2-GEF inactive mutants (F129Y and R172C/L173A) fail to stimulate cell proliferation compared to the wild type-expressing cells. The GEF effect on Ras follows a faster kinetics than other GTPase substrates (such as Rac2 or Rac1) and is a better substrate, too. The GEF action is due to PLD2 (protein) itself, independent of the lipase product PA. PA can still have a fine-tuning regulatory effect on Ras-GTP depending upon its cellular concentration. Rapidly growing human breast cancer cells MDA-MB 231 (but not the slow growing MCF7 counterpart) have high levels of endogenous PLD2-GEF which correlates with high Ras activation. The PLD2-"GEF" activity is even higher than the classical "lipase" activity and is abrogated with GEF single point mutants, particularly F129Y, and concomitantly with a slow rate of cell growth. This can be crucial to cancer biology in that not only Ras mutations explain abnormal growth, but the existence of a new GEF for Ras: a GEF molecule that happens to be a phospholipase.
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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.