GZ-MEDIATED HORMONAL INHIBITION OF CYCLIC-AMP ACCUMULATION

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 alpha-subunits of G(i2) (alpha(i2)) constitutively inhibit cAMP accumulation when transfected into cells. Cells have now been transfected with mutant alpha-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 alpha(z), alpha(i1), and alpha(i3) inhibited cAMP accumulation but alpha(o) did not. Moreover, expression of wild-type alpha(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.