ArticleThe Journal of biological chemistry2011
Kinetic analysis of autotaxin reveals substrate-specific catalytic pathways and a mechanism for lysophosphatidic acid distribution.
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 21 papers.
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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.
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Who cites it
21 citing papers in PubMed, 32 citations in OpenAlex.
- A direct, real-time, spectrophotometric assay for measuring ENPP1-catalyzed cGAMP hydrolysis.The Journal of biological chemistry · 2026Article
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- Identification of a differential metabolite-based signature in patients with late-stage knee osteoarthritis.Osteoarthritis and cartilage open · 2022Article
- Catalysis-Independent ENPP1 Protein Signaling Regulates Mammalian Bone Mass.Journal of bone and mineral research : the official journal of the American Society for Bone and Mineral Research · 2022Article
- Autotaxin impedes anti-tumor immunity by suppressing chemotaxis and tumor infiltration of CD8Cell reports · 2021Article
- Review
- Lysophosphatidic acid produced by autotaxin acts as an allosteric modulator of its catalytic efficiency.The Journal of biological chemistry · 2018Article
- Autotaxin in Pathophysiology and Pulmonary Fibrosis.Frontiers in medicine · 2018Review
- Dysregulation of lysophosphatidic acids in multiple sclerosis and autoimmune encephalomyelitis.Acta neuropathologica communications · 2017Observational
- Steroid binding to Autotaxin links bile salts and lysophosphatidic acid signalling.Nature communications · 2016Article
- Molecular cause and functional impact of altered synaptic lipid signaling due to a prg-1 gene SNP.EMBO molecular medicine · 2016Article
- Regulation of autotaxin expression and secretion by lysophosphatidate and sphingosine 1-phosphate.Journal of lipid research · 2015Article
- Autotaxin: structure-function and signaling.Journal of lipid research · 2014Review
- Molecular basis of purinergic signal metabolism by ectonucleotide pyrophosphatase/phosphodiesterases 4 and 1 and implications in stroke.The Journal of biological chemistry · 2014Article
- Site-directed mutagenesis maps interactions that enhance cognate and limit promiscuous catalysis by an alkaline phosphatase superfamily phosphodiesterase.Biochemistry · 2013Article
- A metabolically-stabilized phosphonate analog of lysophosphatidic acid attenuates collagen-induced arthritis.PloS one · 2013Article
- Non-invasive imaging of tumors by monitoring autotaxin activity using an enzyme-activated near-infrared fluorogenic substrate.PloS one · 2013Article
- Quantitative full time course analysis of nonlinear enzyme cycling kinetics.Scientific reports · 2013Article
- Article
- Article
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Authors and funding
6 authors at 1 institution in 1 country.
Funding
Abstract
Autotaxin (ATX) is a secreted lysophospholipase D that hydrolyzes lysophosphatidylcholine (LPC) into lysophosphatidic acid (LPA), initiating signaling cascades leading to cancer metastasis, wound healing, and angiogenesis. Knowledge of the pathway and kinetics of LPA synthesis by ATX is critical for developing quantitative physiological models of LPA signaling. We measured the individual rate constants and pathway of the LPA synthase cycle of ATX using the fluorescent lipid substrates FS-3 and 12-(N-methyl-N-(7-nitrobenz-2-oxa-1,3-diazol-4-yl))-LPC. FS-3 binds rapidly (k(1) ≥500 μm(-1) s(-1)) and is hydrolyzed slowly (k(2) = 0.024 s(-1)). Release of the first hydrolysis product is random and rapid (≥1 s(-1)), whereas release of the second is slow and rate-limiting (0.005-0.007 s(-1)). Substrate binding and hydrolysis are slow and rate-limiting with LPC. Product release is sequential with choline preceding LPA. The catalytic pathway and kinetics depend strongly on the substrate, suggesting that ATX kinetics could vary for the various in vivo substrates. Slow catalysis with LPC reveals the potential for LPA signaling to spread to cells distal to the site of LPC substrate binding by ATX. An ATX mutant in which catalytic threonine at position 210 is replaced with alanine binds substrate weakly, favoring a role for Thr-210 in binding as well as catalysis. FTY720P, the bioactive form of a drug currently used to treat multiple sclerosis, inhibits ATX in an uncompetitive manner and slows the hydrolysis reaction, suggesting that ATX inhibition plays a significant role in lymphocyte immobilization in FTY720P-based therapeutics.
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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.