PERK2 Antibody

Overview of PERK/EIF2AK3

PERK (EIF2AK3) is a serine/threonine kinase integral to the unfolded protein response (UPR) and integrated stress response (ISR). It phosphorylates eukaryotic initiation factor 2α (eIF2α) at Ser51 under endoplasmic reticulum (ER) stress, attenuating global protein synthesis while promoting selective translation of stress-responsive genes like ATF4 and NRF2 . Dysregulation of PERK signaling is implicated in cancer progression, Wolcott-Rallison syndrome, and oxidative stress disorders .

Key PERK Antibodies and Their Applications

Commercial PERK antibodies are widely used in research for Western blot (WB), immunohistochemistry (IHC), and immunofluorescence (IF). Below is a comparative table of validated antibodies:

Role in Cancer Cell Proliferation

• G2/M Cell Cycle Arrest: PERK knockdown in MDA-MB468 and T47D breast cancer cells delays G2/M progression, reducing BrdU incorporation by 50% and increasing apoptosis .

• Tumor Growth: PERK-deficient MMTV-Neu mice show delayed tumor onset and reduced NRF2 phosphorylation (Thr-80), highlighting PERK’s role in redox homeostasis .

ER Stress and Oxidative Responses

• NQO1 Regulation: PERK silencing in ARPE-19 retinal pigment epithelial cells reduces NRF2 phosphorylation (Ser40) and NQO1 expression, impairing antioxidant responses during ER stress .

• Mitochondrial Function: PERK-mediated UPR enhances mitochondrial oxidative phosphorylation via ATF4-dependent COX7A2L upregulation, promoting respiratory supercomplex formation .

Therapeutic Targeting

• GSK2656157: A PERK inhibitor suppresses pancreatic cancer growth by blocking eIF2α phosphorylation and downstream ATF4/CHOP pathways .

• 125I Radiation: Upregulates PERK-eIF2α-ATF4-CHOP signaling in HepG2 cells, inducing apoptosis reversible by PERK RNAi .

Technical Considerations for PERK Detection

• Band Migration: PERK migrates at ~130–170 kDa in WB due to glycosylation and phosphorylation .

• Phospho-Specific Antibodies: Anti-phospho-T982 (ab192591) is critical for studying PERK activation kinetics under stress .

• Knockout Validation: Use PERK-knockout cell lines (e.g., HeLa PERK-KO) to confirm antibody specificity .

Clinical Implications

• Biomarker Potential: Elevated p-eIF2α and PERK correlate with poor survival in pancreatic ductal adenocarcinoma (PDAC), suggesting prognostic value .

• Wolcott-Rallison Syndrome: PERK mutations disrupt proinsulin trafficking in β-cells, linking ER stress to insulin deficiency .