posted on 2023-06-07, 22:12authored byWilliam J Wolfgang, Ashwini Hoskote, Ian J H Roberts, Shannon Jackson, Michael Forte
One of the best understood signal transduction pathways activated by receptors containing seven transmembrane domains involves activation of heterotrimeric G-protein complexes containing Gs, the subsequent stimulation of adenylyl cyclase, production of cAMP, activation of protein kinase A (PKA), and the phosphorylation of substrates that control a wide variety of cellular responses. Here, we report the identification of "loss-of-function" mutations in the Drosophila Gs gene (dgs). Seven mutants have been identified that are either complemented by transgenes representing the wild-type dgs gene or contain nucleotide sequence changes resulting in the production of altered Gsprotein. Examination of mutant alleles representing loss-of-Gs function indicates that the phenotypes generated do not mimic those created by mutational elimination of PKA. These results are consistent with the conclusion reached in previous studies that activation of PKA, at least in these developmental contexts, does not depend on receptor-mediated increases in intracellular cAMP, in contrast to the predictions of models developed primarily on the basis of studies in cultured cells.
History
Publication status
Published
Journal
Genetics
ISSN
0016-6731
Issue
3
Volume
158
Page range
1189-1201
Pages
13.0
Department affiliated with
Biology and Environmental Science Publications
Notes
Postdoctoral fellow. Designed, initiated and screened 5,000 single Drosophila chromosomes to isolate mutations in Gas. Further genetic characterisation was by other postdoc (Wolfgang) after I left the lab. The first demonstration that G-protein alpha S signalling in multi cellular organisms is protein kinase A independent