G z -Mediated Hormonal Inhibition of Cyclic AMP accumulation

Abstract

Hormones inhibit synthesis of adenosine 3′,5′-monophosphate (cAMP) in most cells via receptors coupled to pertussis toxin (PTX)-sensitive guanine nucleotide-binding (G) proteins. Mutationally activated α subunits of G i2 (α i2 ) constitutively inhibit cAMP accumulation when transfected into cells. Cells have now been transfected with mutant α subunits of four other G proteins—G z , a PTX-insensitive G protein of unknown function, and G i1 , G i3 , and G o , which are PTX-sensitive. Mutant α z , α i1 , and α i3 inhibited cAMP accumulation but α o did not. Moreover, expression of wild-type α z produced cells in which PTX did not block hormonal inhibition of cAMP accumulation. Thus, G z can trigger an effector pathway in response to hormone receptors that ordinarily interact with PTX-sensitive G i proteins.