Identification and biochemical characterization of a novel autotaxin isoform, ATX, with a four-amino acid deletion

Authors: Hashimoto, Takafumi¹; Okudaira, Shinichi¹; Igarashi, Koji²; Hama, Kotaro¹; Yatomi, Yutaka³; Aoki, Junken⁴

Source: The Journal of Biochemistry, Volume 151, Number 1, January 2012 , pp. 89-97(9)

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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 (ATX, and ). In this study, we identified and characterized ATX, a novel alternative splice variant of ATX, which has a four-amino acid deletion in the L2 linker region of ATX. ATX was found to be the second major isoform following ATX and fully active. ATX and ATX showed similar divalent cation sensitivity and cell motility-stimulating activity. ATX and ATX are present in wide range of organism from fish to mammals. Among them, only ATX was found in Gallus gallus and Xenopus laevis, suggesting the indispensable role of the isoform. ATX was expressed in various human tissues with different expression patterns from that of ATX. These results show that ATX is a second major ATX isoform sharing similar biochemical characters with the major isoform, ATX, and is a potential biomarker.

Keywords: alternative splicing; autotoxin; lysophosphatidic acid; lysophosphatidylcholine; lysophospholipase D

Document Type: Regular paper

DOI: http://dx.doi.org/10.1093/jb/mvr126

Affiliations: 1: Department of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Science, Tohoku University, 6-3 Aoba Aramaki, Aoba-ku, Sendai, Miyagi 980-8578; , 2: Bioscience Division, Reagent Development Department, AIA Research Group, TOSOH Corporation, Kanagawa 252-1123; , 3: Department of Clinical Laboratory Medicine, Graduate School of Medicine, The University of Tokyo, 7-3-1 Hongo, Bunkyo-ku, Tokyo 113-8655; and , 4: Department of Molecular and Cellular Biochemistry, Graduate School of Pharmaceutical Science, Tohoku University, 6-3 Aoba Aramaki, Aoba-ku, Sendai, Miyagi 980-8578; , PRESTO, JST, 4-1-8 Honcho, Kawaguchi-shi, Saitama, 332-0012, Japan,

Publication date: 2012-01-01

Identification and biochemical characterization of a novel autotaxin isoform, ATX, with a four-amino acid deletion

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