GTPase inhibiting mutations activate the alpha chain of Gs and stimulate adenylyl cyclase in human pituitary tumours

Nature. 1989 Aug 31;340(6236):692-6. doi: 10.1038/340692a0.

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.

Publication types

  • Research Support, Non-U.S. Gov't
  • Research Support, U.S. Gov't, P.H.S.

MeSH terms

  • Adenylyl Cyclases / metabolism*
  • Amino Acid Sequence
  • Arginine / genetics
  • GTP Phosphohydrolases / antagonists & inhibitors*
  • GTP Phosphohydrolases / genetics
  • GTP-Binding Proteins / genetics*
  • GTP-Binding Proteins / metabolism
  • Glutamine / genetics
  • Humans
  • Mutation*
  • Neoplasm Proteins / genetics
  • Phosphoric Monoester Hydrolases / antagonists & inhibitors*
  • Pituitary Neoplasms / enzymology
  • Pituitary Neoplasms / genetics*
  • Proto-Oncogene Proteins / genetics

Substances

  • Neoplasm Proteins
  • Proto-Oncogene Proteins
  • Glutamine
  • Arginine
  • Phosphoric Monoester Hydrolases
  • GTP Phosphohydrolases
  • GTP-Binding Proteins
  • Adenylyl Cyclases