Activation mechanism of Gi and Go by reactive oxygen species

Motohiro Nishida, Kevin L. Schey, Shuichi Takagahara, Kenji Kontani, Toshiaki Katada, Yasuteru Urano, Tetsuo Nagano, Taku Nagao, Hitoshi Kurose

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47 Citations (Scopus)


Reactive oxygen species are proposed to work as intracellular mediators. One of their target proteins is the a subunit of heterotrimeric GTP-binding proteins (Gαi and Gαo), leading to activation. H2O2 is one of the reactive oxygen species and activates purified Gαi2. However, the activation requires the presence of Fe2+, suggesting that H2O2 is converted to more reactive species such as ·OH. The analysis with mass spectrometry shows that seven cysteine residues (Cys66, Cys112, Cys140, Cys255, Cys287, Cys326, and Cys352) of Gαi2 are modified by the treatment with ·OH. Among these cysteine residues, Cys66, Cys112, Cys140, Cys255, and Cys352 are not involved in ·OH-induced activation of Gαi2. Although the modification of Cys287 but not Cys326 is required for subunit dissociation, the modification of both Cys287 and Cys326 is necessary for the activation of Gαi2 as determined by pertussis toxin-catalyzed ADP-ribosylation, conformation-dependent change of trypsin digestion pattern or guanosine 5′.3-O.(thio)triphosphate binding. Wild type Gαi2 but not Cys287- or Cys326-substituted mutants are activated by UV light, singlet oxygen, superoxide anion, and nitric oxide, indicating that these oxidative stresses activate Gαi2 by the mechanism similar to ·OH-induced activation. Because Cys287 exists only in Gi family, this study explains the selective activation of Gi/Go by oxidative stresses.

Original languageEnglish
Pages (from-to)9036-9042
Number of pages7
JournalJournal of Biological Chemistry
Issue number11
Publication statusPublished - Mar 15 2002
Externally publishedYes

All Science Journal Classification (ASJC) codes

  • Biochemistry
  • Molecular Biology
  • Cell Biology


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