title: Identification and biochemical characterization of a novel autotaxin isoform, ATXδ, with a four-amino acid deletion.
abstract: Autotaxin (ATX) is lysophospholipase D, which converts lysophospholipids such as lysophosphatidylcholine (LPC) to lysophosphatidic acid (LPA), a bioactive lipid mediator with multiple biological roles. ATX is present in high concentrations in various biological fluids and is responsible for LPA production in these fluids. The plasma ATX level is altered in some patho-physiological conditions. Three splicing isoforms of ATX have been reported so far (ATXα, β and γ). In this study, we identified and characterized ATXδ, a novel alternative splice variant of ATX, which has a four-amino acid deletion in the L2 linker region of ATXβ. ATXδ was found to be the second major isoform following ATXβ and fully active. ATXβ and ATXδ showed similar divalent cation sensitivity and cell motility-stimulating activity. ATXβ and ATXδ are present in wide range of organism from fish to mammals. Among them, only ATXδ was found in Gallus gallus and Xenopus laevis, suggesting the indispensable role of the isoform. ATXδ was expressed in various human tissues with different expression patterns from that of ATXβ. These results show that ATXδ is a second major ATX isoform sharing similar biochemical characters with the major isoform, ATXβ, and is a potential biomarker.
authors: Department of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Science, Tohoku University, 6-3 Aoba Aramaki, Aoba-ku, Sendai, Miyagi 980-8578, Japan.
authors: Takafumi
authors: T
authors: Hashimoto
authors: Shinichi
authors: S
authors: Okudaira
authors: Koji
authors: K
authors: Igarashi
authors: Kotaro
authors: K
authors: Hama
authors: Yutaka
authors: Y
authors: Yatomi
authors: Junken
authors: J
authors: Aoki
mesh_terms: D017398:Alternative Splicing; D000595:Amino Acid Sequence; D000596:Amino Acids / Q000235:genetics*; D000818:Animals; D001483:Base Sequence; D055162:Biocatalysis; D015153:Blotting, Western; D003001:Cloning, Molecular; D005260:Female; D020869:Gene Expression Profiling; D015971:Gene Expression Regulation, Enzymologic; D057809:HEK293 Cells; D006801:Humans; D006868:Hydrolysis; D007527:Isoenzymes / Q000235:genetics / Q000378:metabolism; D008244:Lysophosphatidylcholines / Q000378:metabolism; D008246:Lysophospholipids / Q000378:metabolism; D008297:Male; D008969:Molecular Sequence Data; D010727:Phosphoric Diester Hydrolases / Q000235:genetics* / Q000378:metabolism; D020133:Reverse Transcriptase Polymerase Chain Reaction; D017384:Sequence Deletion; D017386:Sequence Homology, Amino Acid; D012689:Sequence Homology, Nucleic Acid; D000099189:Lysophospholipase D
chemical_list: D000596:Amino Acids; D007527:Isoenzymes; D008244:Lysophosphatidylcholines; D008246:Lysophospholipids; D010727:Phosphoric Diester Hydrolases; D000099189:Lysophospholipase D; C032881:lysophosphatidic acid