Common modifications of trimeric G proteins and ras protein: involvement of polyisoprenylation.
The heterotrimeric guanine nucleotide-binding regulatory proteins act at the inner surface of the plasma membrane to relay information from cell surface receptors to effectors inside the cell. These G proteins are not integral membrane proteins, yet are membrane associated. The processing and function of the gamma subunit of the yeast G protein involved in mating-pheromone signal transduction was found to be affected by the same mutations that block ras processing. The nature of these mutations implied that the gamma subunit was polyisoprenylated and that this modification was necessary for membrane association and biological activity. A microbial screen was developed for pharmacological agents that inhibit polyisoprenylation and that have potential application in cancer therapy.
Department of Biochemistry and Molecular Biology, University of Chicago, IL 60637.
A A
AA
Finegold
W R
WR
Schafer
J
J
Rine
M
M
Whiteway
F
F
Tamanoi
D000595:Amino Acid Sequence; D002462:Cell Membrane / Q000378:metabolism; D003001:Cloning, Molecular; D000939:Epitopes / Q000235:genetics; D019204:GTP-Binding Proteins / Q000235:genetics / Q000378:metabolism*; D006389:Hemagglutinins, Viral / Q000276:immunology; D008148:Lovastatin / Q000494:pharmacology; D008798:Mevalonic Acid / Q000494:pharmacology; D008969:Molecular Sequence Data; D009154:Mutation; D015689:Oncogene Protein p21(ras) / Q000235:genetics / Q000378:metabolism*; D009975:Orthomyxoviridae / Q000276:immunology; D011499:Protein Processing, Post-Translational; D012441:Saccharomyces cerevisiae / Q000235:genetics* / Q000378:metabolism; D015398:Signal Transduction; D013489:Suppression, Genetic
D000939:Epitopes; D006389:Hemagglutinins, Viral; D008148:Lovastatin; D019204:GTP-Binding Proteins; D015689:Oncogene Protein p21(ras); D008798:Mevalonic Acid