ArticleThe Journal of biological chemistry2010
Phosphatidic acid is a leukocyte chemoattractant that acts through S6 kinase signaling.
Article in The Journal of biological chemistry, 2010. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 32 papers.
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Who cites it
32 citing papers in PubMed, 43 citations in OpenAlex.
- Multifunctional Thiolated Hyaluronic Acid-graft-PEDOT Dressing With Antifouling, On-Demand Drug Delivery and Electrical Stimulation for Wound Healing.Advanced healthcare materials · 2026Article
- Regulation of Cell Proliferation and Migration by Extracellular Phosphatidic Acid.Biomedicines · 2026Review
- Core Acupoint Prescription Patterns for Primary Dysmenorrhea: Data Mining and Network-Based Analysis.Journal of pain research · 2026Article
- mTORC1 inhibition by sirolimus as adjunctive treatment in experimental pneumococcal meningitis.Brain communications · 2026Article
- Role of mTORC1 Signaling in Regulating the Immune Function of Granulocytes in Teleost Fish.International journal of molecular sciences · 2023Article
- Phosphatidic Acid Stimulates Lung Cancer Cell Migration through Interaction with the LPA1 Receptor and Subsequent Activation of MAP Kinases and STAT3.Biomedicines · 2023Article
- Uncovering the multifaceted roles played by neutrophils in allogeneic hematopoietic stem cell transplantation.Cellular & molecular immunology · 2021Review
- Treatment personalization in gastrointestinal neuroendocrine tumors.Current treatment options in oncology · 2021Review
- Phosphatidic Acid Stimulates Myoblast Proliferation through Interaction with LPA1 and LPA2 Receptors.International journal of molecular sciences · 2021Article
- Morphological and Motility Features of the Stable Bleb-Driven Monopodial Form ofInfection and immunity · 2020Article
- Mammalian phospholipase D: Function, and therapeutics.Progress in lipid research · 2020Review
- Altered adipocyte differentiation and unbalanced autophagy in type 2 Familial Partial Lipodystrophy: an in vitro and in vivo study of adipose tissue browning.Experimental & molecular medicine · 2019Article
- Oxidized LDL phagocytosis during foam cell formation in atherosclerotic plaques relies on a PLD2-CD36 functional interdependence.Journal of leukocyte biology · 2018Article
- A Unique Homeostatic Signaling Pathway Links Synaptic Inactivity to Postsynaptic mTORC1.The Journal of neuroscience : the official journal of the Society for Neuroscience · 2018Article
- VapA of Rhodococcus equi binds phosphatidic acid.Molecular microbiology · 2018Article
- A Phosphatidic Acid (PA) conveyor system of continuous intracellular transport from cell membrane to nucleus maintains EGF receptor homeostasis.Oncotarget · 2016Article
- Membrane Tension Acts Through PLD2 and mTORC2 to Limit Actin Network Assembly During Neutrophil Migration.PLoS biology · 2016Article
- Regulation of innate immune cell function by mTOR.Nature reviews. Immunology · 2015Review
- Phosphatidic Acid Increases Epidermal Growth Factor Receptor Expression by Stabilizing mRNA Decay and by Inhibiting Lysosomal and Proteasomal Degradation of the Internalized Receptor.Molecular and cellular biology · 2015Article
- S6K is a morphogenic protein with a mechanism involving Filamin-A phosphorylation and phosphatidic acid binding.FASEB journal : official publication of the Federation of American Societies for Experimental Biology · 2015Article
Corrections and comments
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Authors and funding
4 authors at 2 institutions in 1 country.
Funding
Abstract
Phosphatidic acid (PA) is a pleiotropic lipid second messenger in mammalian cells. We report here that extracellular PA acts as a leukocyte chemoattractant, as membrane-soluble dioleoyl-PA (DOPA) elicits actin polymerization and chemotaxis of human neutrophils and differentiated proleukemic HL-60 cells. We show that the mechanism for this involves the S6 kinase (S6K) signaling enzyme. Chemotaxis was inhibited >90% by the S6K inhibitors rapamycin and bisindolylmaleimide and by S6K1 silencing using double-stranded RNA. However, it was only moderately ( approximately 30%) inhibited by mTOR siRNA, indicating the presence of an mTOR-independent mechanism for S6K. Exogenous PA led to robust time- and dose-dependent increases in S6K enzymatic activity and Thr(421)/Ser(424) phosphorylation, further supporting a PA/S6K connection. We also investigated whether intracellular PA production affects cell migration. Overexpression of phospholipase D2 (PLD2) and, to a lesser extent, PLD1, resulted in elevation of both S6K activity and chemokinesis, whereas PLD silencing was inhibitory. Because the lipase-inactive PLD2 mutants K444R and K758R neither activated S6K nor induced chemotaxis, intracellular PA is needed for this form of cell migration. Lastly, we demonstrated a connection between extracellular and intracellular PA. Using an enhanced green fluorescent protein-derived PA sensor (pEGFP-Spo20PABD), we showed that exogenous PA or PA generated in situ by bacterial (Streptomyces chromofuscus) PLD enters the cell and accumulates in vesicle-like cytoplasmic structures. In summary, we report the discovery of PA as a leukocyte chemoattractant via cell entry and activation of S6K to mediate the cytoskeletal actin polymerization and leukocyte chemotaxis required for the immune function of these cells.
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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.