GCN2 (E9A9R) Rabbit mAb

Phosphorylation of the eukaryotic initiation factor 2 (eIF2) alpha subunit is a well-documented mechanism of downregulating protein synthesis under a variety of stress conditions. Kinases activated by viral infection (PKR), endoplasmic reticulum stress (PERK/PEK), amino acid deprivation (GCN2), and hemin deficiency (HRI) can phosphorylate the eIF2 alpha subunit (1,2). GCN2 is also required for UV light-induced translation inhibition, and in vivo phosphorylation of murine GCN2 at Thr898 is induced by both UV irradiation and by leucine deprivation (3). UV-induced activation of NF-κB also requires GCN2, which may act simply by preventing translation of IκB-alpha to replace pools that have been ubiquitinated and degraded (4). Interestingly, proteasome inhibitors (MG132 and ALLN) activate the GCN2/eIF2alpha pathway, suggesting a pivotal role for this kinase in stress response and ubiquitin-mediated signaling (5). In vitro autophosphorylation of yeast GCN2 within its activation loop at Thr882 and Thr887 (Thr898 and Thr903 in mouse) has also been reported (6). 1.Kaufman, R.J. (1999) Genes Dev 13, 1211-33. 2.Sheikh, M.S. and Fornace, A.J. (1999) Oncogene 18, 6121-8. 3.Deng, J. et al. (2002) Curr Biol 12, 1279-86. 4.Jiang, H.Y. and Wek, R.C. (2005) Biochem J 385, 371-80. 5.Jiang, H.Y. and Wek, R.C. (2005) J Biol Chem 280, 14189-202. 6.Garcia-Barrio, M. et al. (2002) J Biol Chem 277, 30675-83.