Different single receptor domains determine the distinct G protein coupling profiles of members of the vasopressin receptor family

作者：Liu J; Wess J

来源：JOURNAL OF BIOLOGICAL CHEMISTRY, 1996, 271(15): 8772-8778.

DOI：10.1074/jbc.271.15.8772

The vasopressin receptor family is unique among all classes of peptide receptors in that its individual members couple to different subsets of G proteins. The V-1n vasopressin receptor, for example, is preferentially linked to G proteins of the G(q/11) class (biochemical response: stimulation of phosphatidylinositol hydrolysis), whereas the V-2 vasopressin receptor is selectively coupled to G(s) (biochemical response: stimulation of adenylyl cyclase). To elucidate the structural basis underlying this functional heterogeneity, we have systematically exchanged different intracellular domains between the V-1a and V-2 receptors. Transient expression of the resulting hybrid receptors in COS-7 cells showed that all mutant receptors containing V-1a receptor sequence in the second intracellular loop were able to activate the phosphatidylinositol pathway with high efficiency. On the other hand, only those hybrid receptors containing V-2 receptor sequence in the third intracellular loop were capable of efficiently stimulating cAMP production. These findings suggest that the differential G protein coupling profiles of individual members of a structurally closely related receptor subfamily can be determined by different single intracellular receptor domains.

• 出版日期1996-4-12