Identification of a lysophosphatidylserine receptor on mast cells.
Lysophosphatidyl-L-serine (lysoPS) is thought to be an immunological regulator because it dramatically augments the degranulation of rat peritoneal mast cells (RPMCs). This stimulatory effect may be mediated by a lysoPS receptor, but its molecule has not been identified yet. During a ligand fishing study for the orphan G-protein-coupled receptor 34 (GPR34), we found that lysoPS caused a dose-dependent inhibition of forskolin-stimulated cAMP accumulation in human GPR34-expressing Chinese hamster ovary (CHO/hGPR34) cells. The CHO/hGPR34 cells were unresponsive to other structurally related phospholipids examined. Quantitative real-time-PCR demonstrated that mRNAs of GPR34 are particularly abundant in mast cells. The effective lysoPS concentration for RPMC degranulation was similar to that required for GPR34 activation, and the structural requirement of lysoPS for RPMC degranulation was in good agreement with that observed in CHO/hGPR34 cells. These results suggest that GPR34 is the functional mast cell lysoPS receptor.
Sugo
Tsukasa
T
Frontier Research Laboratories, Pharmaceutical Research Division, Takeda Pharmaceutical Company Limited, 10 Wadai, Tsukuba, Ibaraki 300-4293, Japan. Sugo_Tsukasa@takeda.co.jp
Tachimoto
Hiroshi
H
Chikatsu
Tomoko
T
Murakami
Yuko
Y
Kikukawa
Yuhsuke
Y
Sato
Shuji
S
Kikuchi
Kuniko
K
Nagi
Toshimi
T
Harada
Mioko
M
Ogi
Kazuhiro
K
Ebisawa
Motohiro
M
Mori
Masaaki
M
D000595:Amino Acid Sequence; D000818:Animals; D016466:CHO Cells; D015550:Cell Degranulation / Q000187:drug effects; D003001:Cloning, Molecular; D006224:Cricetinae; D003412:Cricetulus; D004789:Enzyme Activation; D048049:Extracellular Signal-Regulated MAP Kinases / Q000187:drug effects / Q000378:metabolism; D006801:Humans; D008246:Lysophospholipids / Q000378:metabolism* / Q000494:pharmacology; D008297:Male; D008407:Mast Cells / Q000737:chemistry* / Q000187:drug effects; D051379:Mice; D008969:Molecular Sequence Data; D051381:Rats; D017208:Rats, Wistar; D049312:Receptors, Lysophospholipid / Q000378:metabolism*; D016415:Sequence Alignment
C118065:G-protein-coupled receptor 34; D008246:Lysophospholipids; D049312:Receptors, Lysophospholipid; C025059:lysophosphatidylserine; D048049:Extracellular Signal-Regulated MAP Kinases