MOLECULAR PHARMACOLOGY, 47.835-841 (1995). Stimulation of Type II Adenylyl Cyclase by Chemoattractant

The capacity of N-formylmethionyl-leucyl-phenylalanine (fMLP) and C5a receptors to regulate type Il adenylyl cyclase was examined in transient transfection studies. Coexpression of either one of the chemoattractant receptors with type II adeny-lyl cyclase in human embryonic kidney 293 cells allowed the corresponding chemotactic factor to stimulate cAMP accumu-lation in a dose-dependent manner. The chemoattractant-in-duced stimulation of type II adenylyl cyclase was absolutely dependent on the presence of GTP-bound a subunit of G5, as revealed by the coexpression of a5-Q227L, a constitutively activated mutant of a. Stimulation of type II adenylyl cyclase by either fMLP or C5a was mediated via pertussis toxin-sensi-tive G-like proteins, because the response was abrogated by the toxin. The ability of G5 (a pertussis toxin-insensitive G protein that can couple to a number of G-linked receptors) t