Abstract
ONE or more of three Gi proteins, Gi1–3, mediates hormonal inhibition of adenylyl cyclase1–3. Whether this inhibition is mediated by the α or by the βγ subunits of Gi proteins is unclear1,2. Mutations inhibiting the intrinsic GTPase activity of another G protein, the stimulatory regulator of adenylyl cyclase (Gs), con-stitutively activate it by replacing either of two conserved amino acids in its α subunit (αs)4–7. These mutations create the gsp oncogene which is found in human pituitary and thyroid tumours5,8. In a second group of human endocrine tumours, somatic mutations in the a subunit of Gi2 replace a residue cognate to one of those affected by gsp mutations8. This implies that the mutations convert the αi2 gene into a dominantly acting oncogene, called gip2 (ref. 8), and that the mutant αi2 subunits are constitutively active. We have therefore assessed cyclic AMP accumulation in cultured cells which stably or transiently express exogenous wild-type αi2 complementary DNA or either of two mutant αi2 cDNAs. The results show that putatively oncogenic mutations in αi2 constitutively activate the protein's ability to inhibit cAMP accumulation.
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Wong, Y., Federman, A., Pace, A. et al. Mutant α subunits of Gi2 inhibit cyclic AMP accumulation. Nature 351, 63–65 (1991). https://doi.org/10.1038/351063a0
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DOI: https://doi.org/10.1038/351063a0
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