論文

査読有り 筆頭著者 責任著者 国際誌
2007年1月

Spatial expression patterns and biochemical properties distinguish a second myo-inositol monophosphatase IMPA2 from IMPA1

JOURNAL OF BIOLOGICAL CHEMISTRY
  • Tetsuo Ohnishi
  • ,
  • Hisako Ohba
  • ,
  • Kyung-Chang Seo
  • ,
  • Jungkyun Im
  • ,
  • Yumi Sato
  • ,
  • Yoshimi Iwayama
  • ,
  • Tefichi Furuichi
  • ,
  • Sung-Kee Chung
  • ,
  • Takeo Yoshikawa

282
1
開始ページ
637
終了ページ
646
記述言語
英語
掲載種別
研究論文(学術雑誌)
DOI
10.1074/jbc.M604474200
出版者・発行元
AMER SOC BIOCHEMISTRY MOLECULAR BIOLOGY INC

Lithium is used in the clinical treatment of bipolar disorder, a disease where patients suffer mood swings between mania and depression. Although the mode of action of lithium remains elusive, a putative primary target is thought to be inositol monophosphatase (IMPase) activity. Two IMPase genes have been identified in mammals, the well characterized myo-inositol monophosphatase 1 (IMPA1) and myo-inositol monophosphatase 2 (IMPA2). Several lines of genetic evidence have implicated IMPA2 in the pathogenesis of not only bipolar disorder but also schizophrenia and febrile seizures. However, little is known about the protein, although it is predicted to have lithium-inhibitable IMPase activity based on its homology to IMPA1. Here we present the first biochemical study comparing the enzyme activity of IMPA2 to that of IMPA1. We demonstrate that in vivo, IMPA2 forms homodimers but no heterodimers with IMPA1. Recombinant IMPA2 exhibits IMPase activity, although maximal activity requires higher concentrations of magnesium and a higher pH. IMPA2 shows significantly lower activity toward myo-inositol monophosphate than IMPA1. We therefore screened for additional substrates that could be more efficiently dephosphorylated by IMPA2, but failed to find any. Importantly, when using myo-inositol monophosphate as a substrate, the IMPase activity of IMPA2 was inhibited at high lithium and restricted magnesium concentrations. This kinetics distinguishes it from IMPA1. We also observed a characteristic pattern of differential expression between IMPA1 and IMPA2 in a selection of tissues including the brain, small intestine, and kidney. These data suggest that IMPA2 has a separate function in vivo from that of IMPA1.

リンク情報
DOI
https://doi.org/10.1074/jbc.M604474200
PubMed
https://www.ncbi.nlm.nih.gov/pubmed/17068342
Web of Science
https://gateway.webofknowledge.com/gateway/Gateway.cgi?GWVersion=2&SrcAuth=JSTA_CEL&SrcApp=J_Gate_JST&DestLinkType=FullRecord&KeyUT=WOS:000243166500069&DestApp=WOS_CPL
ID情報
  • DOI : 10.1074/jbc.M604474200
  • ISSN : 0021-9258
  • eISSN : 1083-351X
  • PubMed ID : 17068342
  • Web of Science ID : WOS:000243166500069

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