TY - JOUR
T1 - Identification and biochemical characterization of a novel autotaxin isoform, ATXδ, with a four-amino acid deletion
AU - Hashimoto, Takafumi
AU - Okudaira, Shinichi
AU - Igarashi, Koji
AU - Hama, Kotaro
AU - Yatomi, Yutaka
AU - Aoki, Junken
N1 - Funding Information:
The National Institute of Biomedical Innovation; the National Project on Protein Structural and Functional Analyses from the Ministry of Education; Precursory Research for Embryonic
PY - 2012/1
Y1 - 2012/1
N2 - 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.
AB - 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.
KW - alternative splicing
KW - autotoxin
KW - lysophosphatidic acid
KW - lysophosphatidylcholine
KW - lysophospholipase D
UR - http://www.scopus.com/inward/record.url?scp=84855234519&partnerID=8YFLogxK
UR - http://www.scopus.com/inward/citedby.url?scp=84855234519&partnerID=8YFLogxK
U2 - 10.1093/jb/mvr126
DO - 10.1093/jb/mvr126
M3 - Article
C2 - 21994952
AN - SCOPUS:84855234519
VL - 151
SP - 89
EP - 97
JO - Journal of Biochemistry
JF - Journal of Biochemistry
SN - 0021-924X
IS - 1
ER -