The N54 mutant of Gαs has a conditional dominant negative phenotype which suppresses hormone‐stimulated but not basal cAMP levels

The phenotype of a Ser to Asn mutation at position 54 of the alpha subunit of G(s)(N54-alpha(s)) was characterized in transient transfection experiments in COS and HEK293 cells. Expression of either wild type or N54-alpha(s) increased basal cAMP levels. In contrast, expression of wild type alpha(s), potentiated agonist-stimulated cAMP levels, while expression of N54-alpha(s)caused a decrease. Thus, the N54-alpha(s) mutant possesses a conditional dominant negative phenotype, suppressing preferentially hormone-stimulated effects.