Genetic analysis of the Drosophila Gs alpha gene

One of the best understood signal transduction pathways activated by recept ors containing seven transmembrane domains involves activation of heterotri meric G-protein complexes containing Gs alpha, the subsequent stimulation o f adenylyl cyclase, production of cAMP, activation of protein kinase A (PKA ), and the phosphorylation of substrates that control a wide variety of cel lular responses. Here, we report the identification of "loss-of-function" m utations in the Drosophila Gsa: gene (dgs). Seven mutants have been identif ied that are either complemented by transgenes representing the wild-type d gs gene or contain nucleotide sequence changes resulting in the production of altered Gs alpha protein. Examination of mutant alleles representing los s-of-Gs alpha function indicates that the phenotypes generated do not mimic those created by mutational elimination of PKA. These results are consiste nt with the conclusion reached in previous studies that activation of PKA, at least in these developmental contexts, does not depend on receptor-media ted increases in intracellular cAMP, in contrast to the predictions of mode ls developed primarily on the basis of studies in cultured cells.