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

Biochem Biophys Res Commun. 2002 Apr 26;293(1):396-402. doi: 10.1016/S0006-291X(02)00239-5.


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.

MeSH terms

  • Amino Acid Sequence
  • Animals
  • Binding Sites
  • CHO Cells
  • Cloning, Molecular
  • Cricetinae
  • DNA Primers
  • GTP-Binding Proteins / metabolism*
  • Gastrointestinal Hormones / metabolism
  • Humans
  • Ligands
  • Mitogens / metabolism*
  • Molecular Sequence Data
  • Neuropeptides*
  • Polymerase Chain Reaction
  • Rats
  • Receptors, Cell Surface / chemistry
  • Receptors, Cell Surface / genetics
  • Receptors, Cell Surface / metabolism*
  • Sequence Alignment
  • Sequence Homology, Amino Acid
  • Vascular Endothelial Growth Factor, Endocrine-Gland-Derived


  • DNA Primers
  • Gastrointestinal Hormones
  • Ligands
  • Mitogens
  • Neuropeptides
  • PROK1 protein, human
  • PROK2 protein, human
  • Prok2 protein, rat
  • Receptors, Cell Surface
  • Vascular Endothelial Growth Factor, Endocrine-Gland-Derived
  • prokineticin 1, rat
  • GTP-Binding Proteins

Associated data

  • GENBANK/AY089972
  • GENBANK/AY089973
  • GENBANK/AY089974
  • GENBANK/AY089975
  • GENBANK/AY089976
  • GENBANK/AY089983
  • GENBANK/AY089984