Molecular cloning and characterization of another leukotriene B4 receptor.
Leukotriene B(4) is a potent lipid mediator known to be implicated mainly in inflammatory actions. Previous pharmacological studies indicated the existence of only one class of G protein-coupled receptor for leukotriene B(4), for which a candidate gene, namely BLT, had been identified. Here we report the isolation of another gene encoding a functional G protein-coupled receptor for leukotriene B(4), named JULF2. JULF2 is a novel G protein-coupled receptor of 358 amino acids that shares 36.6% amino acid identity with human BLT. According to genomic information, the JULF2 gene is located on the chromosome 14, about 4 kilobases upstream of the BLT gene. During screening of endogenous ligands for JULF2, we found that leukotriene B(4) induced inhibition of forskolin-stimulated cAMP accumulation in Chinese hamster ovary cells, stably expressing JULF2. Additionally, Chinese hamster ovary cells expressing exogenous JULF2 showed chemotactic responses with leukotriene B(4) in a pertussis toxin-sensitive manner. A large amount of JULF2 mRNA was detected in the human spleen and the peripheral blood leukocytes. Furthermore, JULF2 mRNA was expressed in mononuclear lymphocytes, in which BLT mRNA was barely detected. The discovery of this second leukotriene B(4) receptor will eventually lead to a better understanding of the classification of leukotriene B(4) receptors and reconsideration of the pathophysiological role of leukotriene B(4).
Kamohara
M
M
Molecular Medicine Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Tsukuba, Ibaraki 305-8585, Japan. kamohara@yamanouchi.co.jp
Takasaki
J
J
Matsumoto
M
M
Saito
T
T
Ohishi
T
T
Ishii
H
H
Furuichi
K
K
D000595:Amino Acid Sequence; D000818:Animals; D001483:Base Sequence; D016466:CHO Cells; D002633:Chemotaxis / Q000187:drug effects; D003001:Cloning, Molecular; D006224:Cricetinae; D017931:DNA Primers; D006801:Humans; D007975:Leukotriene B4 / Q000494:pharmacology; D008024:Ligands; D008969:Molecular Sequence Data; D012333:RNA, Messenger / Q000235:genetics; D018102:Receptors, Leukotriene B4 / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D017386:Sequence Homology, Amino Acid
D017931:DNA Primers; C485878:LTB4R2 protein, human; D008024:Ligands; D012333:RNA, Messenger; D018102:Receptors, Leukotriene B4; D007975:Leukotriene B4