Isolation and identification of EG-VEGF/prokineticins as cognate ligands for two orphan G-protein-coupled receptors.
Endocrine gland-derived vascular endothelial growth factor (EG-VEGF, identical to prokineticin 1) is a novel peptide recently identified as a selective mitogen for endocrine gland endothelial cells. The present study demonstrates that EG-VEGF/prokineticin 1 and a peptide closely related to EG-VEGF, prokineticin 2, are cognate ligands of two orphan G-protein-coupled receptors designated ZAQ (=EG-VEGF/PK-R1) and I5E (=EG-VEGF/PK-R2). EG-VEGF/prokineticin 1 and prokineticin 2 induced a transient increase in intracellular calcium ion concentration ([Ca(2+)](i)) with nanomolar potency in Chinese hamster ovary (CHO) cells expressing EG-VEGF/PK-R1 and -R2 and bind to these cells with high affinity and with different receptor selectivity. EG-VEGF/prokineticins provoke rapid phosphorylation of p44/42 MAP kinase and DNA synthesis in the bovine adrenal capillary endothelial cells (BACE). The mRNAs of both EG-VEGF/PK-R1 and -R2 were expressed in BACE. The identification of the receptors for EG-VEGF/prokineticins may provide a novel molecular basis for the regulation of angiogenesis in endocrine glands.
Masuda
Yasushi
Y
Pharmaceutical Research Division, Takeda Chemical Industries Ltd., Wadai 10, Tsukuba, Ibaraki 300-4293, Japan.
Takatsu
Yoshihiro
Y
Terao
Yasuko
Y
Kumano
Satoshi
S
Ishibashi
Yoshihiro
Y
Suenaga
Masato
M
Abe
Michiko
M
Fukusumi
Shoji
S
Watanabe
Takuya
T
Shintani
Yasushi
Y
Yamada
Takao
T
Hinuma
Shuji
S
Inatomi
Nobuhiro
N
Ohtaki
Tetsuya
T
Onda
Haruo
H
Fujino
Masahiko
M
D000595:Amino Acid Sequence; D000818:Animals; D001665:Binding Sites; D016466:CHO Cells; D003001:Cloning, Molecular; D006224:Cricetinae; D017931:DNA Primers; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005768:Gastrointestinal Hormones / Q000378:metabolism; D006801:Humans; D008024:Ligands; D008934:Mitogens / Q000378:metabolism*; D008969:Molecular Sequence Data; D009479:Neuropeptides; D016133:Polymerase Chain Reaction; D051381:Rats; D011956:Receptors, Cell Surface / Q000737:chemistry / Q000235:genetics / Q000378:metabolism*; D016415:Sequence Alignment; D017386:Sequence Homology, Amino Acid; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived
D017931:DNA Primers; D005768:Gastrointestinal Hormones; D008024:Ligands; D008934:Mitogens; D009479:Neuropeptides; C467610:PROK1 protein, human; C423608:PROK2 protein, human; C486587:Prok2 protein, rat; D011956:Receptors, Cell Surface; D042662:Vascular Endothelial Growth Factor, Endocrine-Gland-Derived; C467611:prokineticin 1, rat; D019204:GTP-Binding Proteins