ArticleThe Journal of biological chemistry2011
Binding of autotaxin to integrins localizes lysophosphatidic acid production to platelets and mammalian cells.
Article in The Journal of biological chemistry, 2011. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 77 papers.
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Who cites it
77 citing papers in PubMed, 150 citations in OpenAlex.
- Context-dependent lysophosphatidic acid signalling in inflammation: evidence hierarchy, myeloid regulation and translational gaps.Inflammation research : official journal of the European Histamine Research Society ... [et al.] · 2026Review
- The LPC-ATX-LPA-LPAR Axis in Major Depressive Disorder: From PC/LPC Metabolism to Receptor-Active Lipid Signaling.International journal of molecular sciences · 2026Review
- Decoding lysophosphatidic acid signaling in physiology and disease: mapping the multimodal and multinodal signaling networks.Signal transduction and targeted therapy · 2025Review
- Lysophosphatidic Acid Receptors LPAR5 and LPAR2 Inversely Control Hydroxychloroquine-Evoked Itch and Scratching in Mice.International journal of molecular sciences · 2024Article
- Autotaxin-Lysophosphatidate Axis: Promoter of Cancer Development and Possible Therapeutic Implications.International journal of molecular sciences · 2024Review
- Linking the Autotaxin-LPA Axis to Medicinal Cannabis and the Endocannabinoid System.International journal of molecular sciences · 2024Review
- Dysregulated autotaxin expression by T cells in multiple sclerosis.Journal of neuroimmunology · 2024Article
- Autotaxin and Lysophosphatidate Signaling: Prime Targets for Mitigating Therapy Resistance in Breast Cancer.World journal of oncology · 2024Review
- Insights into autotaxin- and lysophosphatidate-mediated signaling in the pancreatic ductal adenocarcinoma tumor microenvironment: a survey of pathway gene expression.American journal of cancer research · 2024Article
- Autotaxin in encephalitogenic CD4 T cells as a therapeutic target for multiple sclerosis.European journal of immunology · 2024Article
- The autotaxin-LPA axis promotes membrane trafficking and secretion in yolk sac visceral endoderm cells.Biology open · 2023Article
- Autotaxin-lysophosphatidic acid receptor 5 axis evokes endothelial dysfunction via reactive oxygen species signaling.Experimental biology and medicine (Maywood, N.J.) · 2023Article
- Ascitic autotaxin as a potential prognostic, diagnostic, and therapeutic target for epithelial ovarian cancer.British journal of cancer · 2023Article
- Influence of Aortic Valve Stenosis and Wall Shear Stress on Platelets Function.Journal of clinical medicine · 2023Review
- Autotaxin inhibitor IOA-289 reduces gastrointestinal cancer progression in preclinical models.Journal of experimental & clinical cancer research : CR · 2023Article
- Autotaxin Inhibition with IOA-289 Decreases Breast Tumor Growth in Mice Whereas Knockout of Autotaxin in Adipocytes Does Not.Cancers · 2023Article
- The Autotaxin-LPA Axis Emerges as a Novel Regulator of Smooth Muscle Cell Phenotypic Modulation during Intimal Hyperplasia.International journal of molecular sciences · 2023Article
- Role of autotaxin in systemic lupus erythematosus.Frontiers in medicine · 2023Review
- Lysophosphatidic acid signaling via LPAJournal of neurochemistry · 2022Article
- Review
17 more citing papers are in PubMed but not listed here.
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Authors and funding
6 authors at 2 institutions in 1 country.
Funding
Abstract
Autotaxin (ATX) is a secreted lysophospholipase D that generates the bioactive lipid mediator lysophosphatidic acid (LPA). We and others have reported that ATX binds to integrins, but the function of ATX-integrin interactions is unknown. The recently reported crystal structure of ATX suggests a role for the solvent-exposed surface of the N-terminal tandem somatomedin B-like domains in binding to platelet integrin αIIbβ(3). The opposite face of the somatomedin B-like domain interacts with the catalytic phosphodiesterase (PDE) domain to form a hydrophobic channel through which lysophospholipid substrates enter and leave the active site. Based on this structure, we hypothesize that integrin-bound ATX can access cell surface substrates and deliver LPA to cell surface receptors. To test this hypothesis, we investigated the integrin selectivity and signaling pathways that promote ATX binding to platelets. We report that both platelet β1 and β3 integrins interact in an activation-dependent manner with ATX via the SMB2 domain. ATX increases thrombin-stimulated LPA production by washed platelets ~10-fold. When incubated under conditions to promote integrin activation, ATX generates LPA from CHO cells primed with bee venom phospholipase A(2), and ATX-mediated LPA production is enhanced more than 2-fold by CHO cell overexpression of integrin β(3). The effects of ATX on platelet and cell-associated LPA production, but not hydrolysis of small molecule or detergent-solubilized substrates, are attenuated by point mutations in the SMB2 that impair integrin binding. Integrin binding therefore localizes ATX activity to the cell surface, providing a mechanism to generate LPA in the vicinity of its receptors.
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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.