Hydrolyzes lysophospholipids to produce the signaling molecule lysophosphatidic acid (LPA) in extracellular fluids. Major substrate is lysophosphatidylcholine. Also can act on sphingosylphosphorylcholine producing sphingosine-1-phosphate, a modulator of cell motility. Can hydrolyze, in vitro, bis-pNPP, to some extent pNP-TMP, and barely ATP. Involved in several motility-related processes such as angiogenesis and neurite outgrowth. Acts as an angiogenic factor by stimulating migration of smooth muscle cells and microtubule formation. Stimulates migration of melanoma cells, probably via a pertussis toxin-sensitive G protein. May have a role in induction of parturition. Possible involvement in cell proliferation and adipose tissue development (Probable). Tumor cell motility-stimulating factor. Required for LPA production in activated platelets, cleaves the sn-1 lysophospholipids to generate sn-1 lysophosphatidic acids containing predominantly 18:2 and 20:4 fatty acids. Shows a preference for the sn-1 to the sn-2 isomer of 1-O-alkyl-sn-glycero-3-phosphocholine (lyso-PAF).

1. Data show that autotaxin (ATX)-mediated autocrine lipid signaling promotes naive pluripotency by intersecting with LIF and BMP4 signaling. PMID: 27738243
2. This study showed that alternative autotaxin-independent pathways are likely responsible for local generation of lysophosphatidic acid in the injured lung. PMID: 27006447
3. Hepatocyte autotaxin expression promotes liver fibrosis and liver cancer. PMID: 27981605
4. These results indicate that ATX-lysophosphatidic acid-LPA3 signaling at the embryo-epithelial boundary induces decidualization via the canonical HB-EGF and COX-2 pathways. PMID: 28588064
5. ATX is required for the development and maintenance of dermal fibrosis in a mouse model of bleomycin-induced systemic scleroderma (SSc) and enables 2 major mediators of SSc fibrogenesis, lysophosphatidic acid and IL-6, to amplify the production of each other. PMID: 27390295
6. These results suggest that the post-transcriptional regulation of ATX expression by HuR and AUF1 modulates cancer cell migration. PMID: 27784781
7. inducible, ubiquitous genetic deletion of ATX in adult mice, as well as long-term potent pharmacologic inhibition, are well tolerated, alleviating potential toxicity concerns of ATX therapeutic targeting. PMID: 26569406
8. findings indicate that the ATX level must be carefully regulated to ensure coordinated vascular formation PMID: 25992708
9. Autotaxin is an inflammatory mediator and therapeutic target in thyroid cancer PMID: 26037280
10. These findings identify ATX and LPA2 as radiation-regulated genes that appear to play a physiological role in DNA repair. PMID: 26027517
11. The results are discussed in terms of ATX regulation in wound healing and cancer.We, therefore, demonstrate the concept that accumulation of LPA in the circulation decreases ATX production PMID: 25896349
12. blocking tumor-driven inflammation by ATX inhibition is effective in decreasing tumor growth in breast cancers where the cancer cells express negligible ATX. PMID: 26071407
13. ATX expression and lysophosphatidic acid production are significantly enhanced in LPS treated BV-2 cells. PMID: 25053164
14. Enpp2(+/-) mice and adipocyte-specific Enpp2 knockout mice fed a high-fat diet showed smaller weight gains and less insulin resistance than control mice, as well as more functionally active brown adipose tissue and increased energy expenditure. PMID: 24969110
15. Autotaxin generates lysophosphatidic acid from lysophophatidylcholine. The role of this pathway in T-lymphocyte homing, inflammation, and airway remodeling is studied and inhibitors are tested. Review. PMID: 24443508
16. Autotaxin signaling governs phenotypic heterogeneity in visceral and parietal mesothelia. PMID: 23936085
17. We validate Enpp2/Autotaxin as one of the highest expressed signature genes in postnatal dermal papilla. PMID: 23677168
18. We investigated the involvement of ATX in inflammatory bowel disease patients and two murine models of colitis. In the T-cell-transferred mouse model, ATX mRNA expression level gradually increased as colitis developed. PMID: 23478591
19. Constitutive lymphocyte transmigration across the basal lamina of high endothelial venules is regulated by the autotaxin/lysophosphatidic acid axis. PMID: 23365076
20. ATX and its enzymatic product lysophosphatidic acid influence lymphocyte migration upon and across an endothelial substratum under physiologic shear stress conditions. PMID: 22962684
21. Data suggest that ATX is a negative regulator of brown fat adipogenesis; inhibition of ATX promotes differentiation of brown adipocytes from cultured embryonic fibroblasts. PMID: 22474126
22. Autotaxin expression from synovial fibroblasts is essential for the pathogenesis of modeled arthritis. PMID: 22493518
23. the ATX-LPA-LPAR axis is a critical regulator of embryonic vascular development that is conserved in vertebrates PMID: 21971049
24. The results suggested a significant role for ATX in lung epithelial cell migration and remodelling through its ability to induce LPA production-mediated phosphorylation of PKCdelta and cortactin. PMID: 21696367
25. Adipose-autotaxin is a negative regulator of fat mass expansion in response to an high-fat diet and contributes to plasma lysophosphatidic acid levels. PMID: 21421848
26. The study reports the crystal structures of mouse ATX alone and in complex with lysophosphatidic acids with different acyl-chain lengths and saturations. PMID: 21240269
27. autotaxin controls bone metastasis formation in mouse through lysophosphatidic acid-dependent activation of osteoclasts PMID: 20305819
28. These results suggest that lysophosphatidic acid, which is converted from lysophosphatidylcholine by ATX, activates LPA1 receptors and induces dorsal root demyelination following nerve injury, which causes neuropathic pain. PMID: 21062487
29. These results reveal the signal transduction defects that underlie the abnormalities in Enpp2(-/-) embryos. PMID: 20692235
30. autotaxin has a role in the development of adipose tissue and obesity-associated pathologies PMID: 12642576
31. Up-regulation of adipocyte autotaxin expression, which could be related to the severe type 2 diabetes phenotype and adipocyte insulin resistance. PMID: 15700135
32. Furthermore, the effect of ATX in preventing apoptosis appears to be mediated through the G-protein-coupled receptor pathway followed by the activation of phosphoinositide 3-kinase and Akt pathway leading to enhanced cell survival. PMID: 16219296
33. These results reveal a critical role for ATX in vascular development, indicate that ATX is the major LPA-producing enzyme in vivo, and suggest that the vascular defects in ATX-deficient embryos may be explained by loss of LPA signaling through Galpha13. PMID: 16782887
34. ATX has a role in stabilizing vessels through novel LPA signaling pathways PMID: 16829511
35. Non-conserved roles for ATX during neural development and organogenesis. PMID: 17366625
36. ATX deletion is lethal at an early stage of the development PMID: 17628547
37. In vivo, an extracellular lysophospholipase D such as murine autotaxin may participate in leiomyoma growth through local lysophosphatidic acid formation. PMID: 18024704
38. Murine and human autotaxin alpha, beta, and gamma isoforms: gene organization, tissue distribution, and biochemical characterization. PMID: 18175805
39. These findings suggest that lysophosphatidic acid (LPA) biosynthesis through ATX is the source of LPA for LPA1 receptor-mediated neuropathic pain. PMID: 18261210
40. Facilitates the entry of lymphocytes from the blood into secondary lymphoid organs. PMID: 18327261
41. Functional ATX is selectively expressed in high endothelial venules (HEVs) of both lymph nodes and Peyer's patches. PMID: 18818380
42. LPA production by autotaxin/lysoPLD regulates murine hemostasis and thrombosis and suggest that binding of autotaxin/lysoPLD to activated platelets may provide a mechanism to localize LPA production. PMID: 19139100
43. Enpp2 is a candidate gene controlling lung function development in mice. PMID: 17804602

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Secreted.

Nucleotide pyrophosphatase/phosphodiesterase family

Expressed in brain and adipose tissue.

KEGG: mmu:18606

UniGene: Mm.250256