Molecular cloning and characterization of prokineticin receptors.
Recent studies have identified two novel biofunctional proteins, termed prokineticin 1/EG-VEGF and prokineticin 2, which were mammalian homologues of mamba MIT1 and frog Bv8. Prokineticins have been demonstrated to exert their physiological functions through G-protein coupled receptors (GPCRs). In this study, we report the molecular identification of two endogenous prokineticin receptors, designated PK-R1 and PK-R2, through a search of the human genomic DNA database. PK-R1, locating in chromosome 2, and PK-R2, locating in chromosome 20p13, shared 87% homology, which was an extremely high value among known GPCRs. In functional assays, mammalian cells expressing PK-Rs responded to prokineticins in a concentration-dependent manner. Tissue distribution analysis revealed that expression of PK-R1 was observed in the testis, medulla oblongata, skeletal muscle and skin, while that of PK-R2 showed preferential expression in the central nervous system. The tissue distribution of PK-Rs reported in this paper suggests that the prokineticins play multifunctional roles in vivo.
Soga
Takatoshi
T
Molecular Medicine Laboratories, Institute for Drug Discovery Research, Yamanouchi Pharmaceutical Co., Ltd., 21 Miyukigaoka, Ibaraki 305-8585, Tsukuba, Japan.
Matsumoto
Shun ichiro
Si
Oda
Tamaki
T
Saito
Tetsu
T
Hiyama
Hideki
H
Takasaki
Jun
J
Kamohara
Masazumi
M
Ohishi
Takahide
T
Matsushime
Hitoshi
H
Furuichi
Kiyoshi
K
D000595:Amino Acid Sequence; D001921:Brain / Q000378:metabolism; D003001:Cloning, Molecular; D018076:DNA, Complementary / Q000096:biosynthesis / Q000737:chemistry; D005768:Gastrointestinal Hormones / Q000096:biosynthesis / Q000378:metabolism; D017930:Genes, Reporter; D006801:Humans; D008156:Luciferases / Q000235:genetics; D008297:Male; D008969:Molecular Sequence Data; D009479:Neuropeptides; D016133:Polymerase Chain Reaction; D012333:RNA, Messenger / Q000032:analysis; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide / Q000737:chemistry / Q000235:genetics* / Q000378:metabolism; D013737:Testis / Q000378:metabolism
D018076:DNA, Complementary; D005768:Gastrointestinal Hormones; D009479:Neuropeptides; C423608:PROK2 protein, human; C470837:PROKR1 protein, human; C470838:PROKR2 protein, human; D012333:RNA, Messenger; D011956:Receptors, Cell Surface; D043562:Receptors, G-Protein-Coupled; D018000:Receptors, Peptide; D008156:Luciferases