GTPase-inhibiting mutations activate the alpha-chain of Gs in human tumours.
Several trophic hormones transmit their signals by coupling to G-proteins. A subset of human growth hormone (GH)-secreting pituitary tumours, characterized by elevated GH secretion, cyclic AMP levels, and adenylyl cyclase activity, carries mutations in the gene that encodes the alpha-chain of Gs. By substitution of a single amino acid (Arg-201 or Gln-227), these mutations inhibit the intrinsic GTPase activity of alpha s, thus stabilizing the protein in its active conformation. The discovery of mutant alpha s proteins in human tumours suggests that the alpha s gene can be converted into an oncogene, called gsp, in cells that proliferate in response to cyclic AMP. Most likely, oncogenes can result from similar mutations in other G-protein alpha-chain genes.
Vallar
L
L
Department of Pharmacology, C.N.R. Center of Cytopharmacology, Scientific Institute San Raffaele, University of Milan, Italy.
D020558:GTP Phosphohydrolases / Q000235:genetics*; D019204:GTP-Binding Proteins / Q000235:genetics / Q000502:physiology*; D006801:Humans; D009154:Mutation / Q000235:genetics; D009857:Oncogenes / Q000235:genetics; D010911:Pituitary Neoplasms / Q000235:genetics* / Q000378:metabolism
D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins