The difficult challenge of cloning the angiotensin II receptor

The vasopressor peptide angiotensin II exerts its cellular effects through a membrane-bound receptor coupled to a G protein. Biochemical and pharmacological analyses of this receptor already identify two different membrane-bound receptors and one cytosoluble angiotensin-II-binding protein. Nevertheless, the purification of the membrane-bound form(s) appears to be difficult. In the absence of purified protein, two cloning strategies of the gene have been explored: (1) expression cloning, identifying the functions of the protein expressed from a cDNA library in COS cells or Xenopus oocytes, has been unsuccessful until now; (2) analogical cloning, trying to identify related members of the seven transmembrane segment receptor family, which could be related to angiotensin receptors, identifies the mas oncogene and two related genes. However, there are accumulating data to exclude their involvement in angiotensin binding.