Identification and characterization of a novel human sphingosine-1-phosphate phosphohydrolase, hSPP2.
Sphingosine 1-phosphate (S1P) is a bioactive lipid molecule that acts as both an extracellular signaling mediator and an intracellular second messenger. S1P is synthesized from sphingosine by sphingosine kinase and is degraded either by S1P lyase or by S1P phosphohydrolase. Recently, mammalian S1P phosphohydrolase (SPP1) was identified and shown to constitute a novel lipid phosphohydrolase family, the SPP family. In this study we have identified a second human S1P phosphohydrolase, SPP2, based on sequence homology to human SPP1. SPP2 exhibited high phosphohydrolase activity against S1P and dihydrosphingosine 1-phosphate. The dihydrosphingosine-1-phosphate phosphohydrolase activity was efficiently inhibited by excess S1P but not by lysophosphatidic acid, phosphatidic acid, or glycerol 3-phosphate, indicating that SPP2 is highly specific to sphingoid base 1-phosphates. Immunofluorescence microscopic analysis demonstrated that SPP2 is localized to the endoplasmic reticulum. Although the enzymatic properties and localization of SPP2 were similar to those of SPP1, the tissue-specific expression pattern of SPP2 was different from that of SPP1. Thus, SPP2 is another member of the SPP family that may play a role in attenuating intracellular S1P signaling.
Ogawa
Chie
C
Department of Biomembrane and Biofunctional Chemistry, Graduate School of Pharmaceutical Sciences, Hokkaido University, Kita 12-jo, Nishi 6-choume, Kita-ku, Sapporo 060-0812, Japan.
Kihara
Akio
A
Gokoh
Maiko
M
Igarashi
Yasuyuki
Y
D000595:Amino Acid Sequence; D006801:Humans; D008565:Membrane Proteins; D008856:Microscopy, Fluorescence; D008969:Molecular Sequence Data; D010744:Phosphoric Monoester Hydrolases / Q000737:chemistry* / Q000235:genetics / Q000502:physiology; D012333:RNA, Messenger / Q000032:analysis; D013379:Substrate Specificity
D008565:Membrane Proteins; D012333:RNA, Messenger; C498527:SGPP1 protein, human; C498526:SGPP2 protein, human; C401298:sphingosine-1-phosphate phosphatase; D010744:Phosphoric Monoester Hydrolases