The Phospho-GCN2 (Thr667) antibody is a specialized tool for detecting the activated form of General Control Nonderepressible 2 (GCN2), a serine/threonine kinase central to cellular stress responses. GCN2 is activated under amino acid deprivation, ultraviolet radiation, or viral infection, primarily through phosphorylation at its conserved Thr667 residue located in the kinase domain. This phosphorylation event triggers conformational changes, enabling GCN2 to phosphorylate eukaryotic initiation factor 2 alpha (eIF2α), which globally suppresses protein synthesis while promoting selective translation of stress-responsive mRNAs (e.g., ATF4).
The antibody specifically recognizes GCN2 when phosphorylated at Thr667. allowing researchers to monitor GCN2 activation status in studies involving nutrient sensing, unfolded protein response, or immune regulation. It is commonly used in Western blotting, immunofluorescence, or immunoprecipitation across human, mouse, and rat samples. Validation typically includes knockout controls or phosphatase treatment to confirm phosphorylation-dependent signals.
Applications span cancer research (tumor adaptation to nutrient scarcity), neurodegenerative diseases (misfolded protein stress), and metabolic disorders. Proper experimental controls, such as amino acid starvation (e.g., histidinol treatment), are recommended to induce phosphorylation. This antibody is critical for elucidating GCN2's role in stress adaptation pathways and therapeutic targeting.