Phospho-GCN2 (T899) antibody is a specialized tool used to detect the activated form of General Control Nonderepressible 2 (GCN2), a serine/threonine kinase critical in cellular stress responses. GCN2 plays a central role in the integrated stress response (ISR), particularly under amino acid deprivation. When cells experience nutrient scarcity, uncharged tRNA accumulates, activating GCN2 via its histidyl-tRNA synthetase-related domain. This triggers autophosphorylation at Thr899 (human GCN2; Thr898 in mice), a key regulatory site required for kinase activity. Phosphorylated GCN2 then phosphorylates eukaryotic initiation factor 2α (eIF2α), reducing global protein synthesis while promoting selective translation of stress-response genes.
The Phospho-GCN2 (T899) antibody specifically recognizes this phosphorylated epitope, enabling researchers to study GCN2 activation dynamics in conditions like nutrient deficiency, oxidative stress, or viral infection. It is widely used in techniques such as Western blotting, immunofluorescence, and immunoprecipitation to investigate stress signaling pathways in cancer, neurodegeneration, and metabolic disorders. Validation typically includes testing in GCN2-knockout models or cells treated with GCN2 activators (e.g., histidinol) to confirm specificity. Proper controls, such as phosphatase treatment to abolish signal, are essential for accurate interpretation. This antibody has become vital for dissecting the molecular mechanisms of cellular adaptation to environmental challenges and exploring therapeutic strategies targeting the ISR pathway.