The Phospho-IRE1 (Ser724) antibody detects the activated form of Inositol-Requiring Enzyme 1 (IRE1), a key sensor in the unfolded protein response (UPR) pathway. IRE1 is a transmembrane serine/threonine kinase-endoribonuclease located in the endoplasmic reticulum (ER). Under ER stress, misfolded proteins accumulate, triggering IRE1 autophosphorylation at Ser724 (human; corresponds to Ser729 in mice), which induces its dimerization/oligomerization and activation. This phosphorylation event is critical for IRE1's RNase activity, enabling cleavage of XBP1 mRNA to generate a spliced transcription factor (XBP1s) that upregulates genes involved in protein folding, degradation, and ER homeostasis.
The Phospho-IRE1 (Ser724) antibody is widely used to study ER stress in diseases such as cancer, neurodegenerative disorders, and diabetes. It specifically recognizes the phosphorylated Ser724 residue, allowing researchers to distinguish activated IRE1 from its inactive form. Validated in techniques like Western blotting, immunofluorescence, and immunohistochemistry, this antibody helps assess IRE1 signaling dynamics in cell lines, tissues, or disease models. Cross-reactivity varies depending on the host species and antibody design, so validation in specific experimental systems is essential. Understanding IRE1 activation via this antibody provides insights into cellular stress responses and therapeutic targeting of UPR-related pathologies.