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Isolation and identification of EG-VEGF/prokineticins as cognate ligands for two orphan G-protein-coupled receptors

2002; Elsevier BV; Volume: 293; Issue: 1 Linguagem: Inglês

10.1016/s0006-291x(02)00239-5

1090-2104

Yasushi Masuda, Yoshihiro Takatsu, Yasuko Terao, Satoshi Kumano, Yoshihiro Ishibashi, Masato Suenaga, Masahiko Abe, Shoji Fukusumi, Takuya Watanabe, Yasushi Shintani, Takao Yamada, Shuji Hinuma, Nobuhiro Inatomi, Tetsuya Ohtaki, Haruo Onda, Masahiko Fujino,

Regulation of Appetite and Obesity

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.