G PROTEINS ROS Targets G Proteins

Abstract:

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 ß-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 ß subunits. In crude membrane preparations from neonatal myocytes, exposure to H₂O₂ increased the proportion of G_o and G_i in the active (trypsin-insensitive) conformation. Exposure of purified G_o to H₂O₂ appeared to cause subunit dissociation and enhanced binding of guanosine 5'-O-(3'-triotriphosphate) (GTP--S) in a manner not reversible by the antioxidant N-acetyl-L-cysteine. Separate exposure of or ß subunits revealed only the 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) G_i and G_o are target proteins of reactive oxygen species. Nature 408: 492-495. [Online Journal]