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Autotaxin Hydrolyzes Sphingosylphosphorylcholine to Produce the Regulator of Migration, Sphingosine-1-Phosphate

 Timothy Clair  ;  Junken Aoki  ;  Mary L. Stracke  ;  Lance A. Liotta  ;  Elliott Schiffmann  ;  Gordon B. Mills  ;  Malgorzata M. Ptaszynska  ;  Suk Woo Nam  ;  Russell W. Bandle  ;  Eunjin Koh 
 CANCER RESEARCH, Vol.63(17) : 5446-5453, 2003 
Journal Title
Issue Date
3T3 Cells ; Animals ; COS Cells ; Catalysis ; Cell Movement/physiology ; Cercopithecus aethiops ; Glucose-6-Phosphate Isomerase/pharmacology* ; Glycoproteins/pharmacology* ; Hydrolysis/drug effects ; Lysophospholipids* ; Mice ; Multienzyme Complexes* ; Phosphodiesterase I ; Phosphoric Diester Hydrolases ; Phosphorylcholine/analogs & derivatives* ; Phosphorylcholine/metabolism* ; Pyrophosphatases ; Receptors, Cell Surface/biosynthesis ; Receptors, G-Protein-Coupled* ; Receptors, Lysophospholipid ; Sphingosine/analogs & derivatives* ; Sphingosine/biosynthesis* ; Sphingosine/metabolism* ; rho GTP-Binding Proteins/metabolism
Autotaxin (ATX) is an exoenzyme that potently induces tumor cell motility, and enhances experimental metastasis and angiogenesis. ATX was shown recently to be identical to serum lysophospholipase D activity, producing lysophosphatidic acid (LPA) from lyso-glycerophospholipids. LPA, itself a strong chemoattractant for tumor cells, may mediate the actions of ATX. We now extend the substrate specificity to sphingosylphosphorylcholine (SPC), which ATX hydrolyzes to sphingosine-1-phosphate (S1P). Under migration assay conditions, this novel reaction for the production of S1P has a substrate (SPC) K(m) = 0.23 +/- 0.07 mM. In our responder cell lines (NIH3T3 clone7 and A2058), S1P exerts maximal biological effects at concentrations of 10-100 nM and is mimicked in its biological effects by ATX plus SPC. These effects include inhibition of ATX- and LPA-stimulated motility, and elevation of activated Rho. In NIH3T3 clone7 cells stimulated with platelet-derived growth factor and treated with 10-25 nM S1P, motility is not inhibited and activation of Rho is unaffected, indicating that S1P possesses specificity in its effects. The exoenzyme ATX can potentially regulate diverse processes such as motility and angiogenesis via the S1P family of receptors. Because ATX hydrolyzes nucleotides, lyso-glycerophospholipids, and phosphosphingolipids into bioactive products, it possesses the ability, depending on the availability of substrates, to act as positive or negative regulator of receptor-mediated activity in the cellular microenvironment.
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1. College of Medicine (의과대학) > Dept. of Biochemistry and Molecular Biology (생화학-분자생물학교실) > 1. Journal Papers
Yonsei Authors
Koh, Eun Jin(고은진) ORCID logo https://orcid.org/0000-0001-8967-6266
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