ROS Targets G Proteins

Abstract

Reactive oxygen species (ROS), such as H 2 O 2 , 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 H 2 O 2 -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 H 2 O 2 increased the proportion of Gα o and Gα i in the active (trypsin-insensitive) conformation. Exposure of purified G o to H 2 O 2 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 H 2 O 2 . 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) Gα i and Gα o are target proteins of reactive oxygen species. Nature 408 : 492-495. [Online Journal]