title: GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours.
abstract: A subset of growth hormone-secreting human pituitary tumours carries somatic mutations that inhibit GTPase activity of a G protein alpha chain, alpha(s). The resulting activation of adenylyl cyclase bypasses the cells' normal requirement for trophic hormone. Amino acids substituted in the putative gsp oncogene identify a domain of G protein alpha-chains required for intrinsic ability to hydrolyse GTP. This domain may serve as a built-in counter-part of the separate GTPase-activating proteins required for GTP hydrolysis by small GTP-binding proteins such as p21ras.
authors.affiliation: Department of Pharmacology, University of California, San Francisco 94143.
authors.forename: C A
authors.initials: CA
authors.lastname: Landis
authors.forename: S B
authors.initials: SB
authors.lastname: Masters
authors.forename: A
authors.initials: A
authors.lastname: Spada
authors.forename: A M
authors.initials: AM
authors.lastname: Pace
authors.forename: H R
authors.initials: HR
authors.lastname: Bourne
authors.forename: L
authors.initials: L
authors.lastname: Vallar
mesh_terms: D000262:Adenylyl Cyclases / Q000378:metabolism*; D000595:Amino Acid Sequence; D001120:Arginine / Q000235:genetics; D020558:GTP Phosphohydrolases / Q000037:antagonists & inhibitors* / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics* / Q000378:metabolism; D005973:Glutamine / Q000235:genetics; D006801:Humans; D009154:Mutation; D009363:Neoplasm Proteins / Q000235:genetics; D010744:Phosphoric Monoester Hydrolases / Q000037:antagonists & inhibitors*; D010911:Pituitary Neoplasms / Q000201:enzymology / Q000235:genetics*; D011518:Proto-Oncogene Proteins / Q000235:genetics
chemical_list: D009363:Neoplasm Proteins; D011518:Proto-Oncogene Proteins; D005973:Glutamine; D001120:Arginine; D010744:Phosphoric Monoester Hydrolases; D020558:GTP Phosphohydrolases; D019204:GTP-Binding Proteins; D000262:Adenylyl Cyclases