Editors' ChoiceG Proteins

ROS Targets G Proteins

Science's STKE  28 Nov 2000:
Vol. 2000, Issue 60, pp. tw2
DOI: 10.1126/stke.2000.60.tw2

Reactive oxygen species (ROS), such as H2O2, can cause activation of tyrosine kinases, small guanosine triphosphatases, and the mitogen-activated protein kinase ERK (extracellular signal-regulated kinase). Nishida et al. propose that direct targets of ROS include alpha subunits of heterotrimeric guanine nucleotide-binding proteins (G proteins). In their experiments, overexpression of the COOH-terminus of the β-adrenergic receptor kinase in rat neonatal cardiomyocytes inhibited H2O2-induced activation of ERK, Akt (another kinase), and Src (a tyrosine kinase), presumably by sequestering G protein βγ subunits. In crude membrane preparations from neonatal myocytes, exposure to H2O2 increased the proportion of Gαo and Gαi in the active (trypsin-insensitive) conformation. Exposure of purified Go to H2O2 appeared to cause subunit dissociation and enhanced binding of guanosine 5'-O-(3'-triotriphosphate) (GTP-γ-S) in a manner not reversible by the antioxidant N-acetyl-L-cysteine. Separate exposure of α or βγ subunits revealed only the α subunits to be sensitive to H2O2. Activation of ERKs and Akt is associated with cell survival, and the authors suggest that signaling through G proteins could help cells adapt to oxidative stress.

Nishida, M., Maruyama, Y., Tanaka, R., Kontani, K., Nagao, T. and Kurose, H. (2000) Gαi and Gαo are target proteins of reactive oxygen species. Nature 408: 492-495. [Online Journal]