Phospho-PERK (Thr980) Antibody [E16F3]

Application: Reactivity: Mouse, Rat

Usage Information

Dilution
WB1:1000

Application
WB

Reactivity
Mouse, Rat

Source
Rabbit Monoclonal Antibody

Storage Buffer
PBS, pH 7.2+50% Glycerol+0.05% BSA+0.01% NaN3

Storage (from the date of receipt)
-20°C (avoid freeze-thaw cycles), 2 years

Predicted MW
170 kDa

Positive Control	AR42J cells (thapsigargin, 1 μM, 20 min)
Negative Control	AR42J cells

Datasheet & SDS

Biological Description

Specificity
Phospho-PERK (Thr980) Antibody [E16F3] detects endogenous levels of total PERK protein only when it is phosphorylated at Thr980.

Clone
E16F3

Synonym(s)
Eukaryotic translation initiation factor 2-alpha kinase 3; PRKR-like endoplasmic reticulum kinase; Pancreatic eIF2-alpha kinase; Protein tyrosine kinase EIF2AK3; Eif2ak3; Pek; Perk

Background
Phospho-PERK Thr980 marks the activated state of protein kinase-like endoplasmic reticulum kinase (PERK), a type I transmembrane eIF2α kinase of the unfolded protein response (UPR) that transduces ER stress from its N-terminal luminal sensor domain through a single transmembrane helix to its C-terminal cytoplasmic kinase domain, where Thr980 autophosphorylation on the activation loop stabilizes the catalytically competent conformation. The kinase domain adopts a canonical bilobal fold with the Thr980 phosphate forming charge-charge interactions with Lys631/Arg634 in the αC helix and Arg934 in the C-lobe, rigidifying the activation loop (residues 953–990, partially disordered) and ordering helix αG to create the eIF2α substrate-binding surface, while luminal domain oligomerization by misfolded proteins drives a "line-up" trans-autophosphorylation mechanism between adjacent PERK dimers. Activated pThr980-PERK phosphorylates eIF2α at Ser51, globally attenuating cap-dependent translation while selectively upregulating ATF4 translation via uORF1 bypass, triggering integrated stress response (ISR) genes for antioxidant defense such as NRF2, protein folding chaperones, amino acid metabolism, and autophagy to restore ER proteostasis under accumulation of unfolded proteins from nutrient deprivation, redox imbalance, or calcium dysregulation. This adaptive pathway protects secretory cells like pancreatic β-cells from ER overload during development and glucose stimulation; pathologically, chronic hyperactivation exhausts adaptation, leading to apoptosis via CHOP/ATF4 induction in diabetes (β-cell failure), neurodegeneration such as Alzheimer's and prion diseases, and ischemia-reperfusion injury, while PERK loss impairs the UPR, causing proinsulin misfolding. Therapeutic PERK inhibitors show promise in prion disease and cancer by blocking ISR-driven survival.

Background

Phospho-PERK Thr980 marks the activated state of protein kinase-like endoplasmic reticulum kinase (PERK), a type I transmembrane eIF2α kinase of the unfolded protein response (UPR) that transduces ER stress from its N-terminal luminal sensor domain through a single transmembrane helix to its C-terminal cytoplasmic kinase domain, where Thr980 autophosphorylation on the activation loop stabilizes the catalytically competent conformation. The kinase domain adopts a canonical bilobal fold with the Thr980 phosphate forming charge-charge interactions with Lys631/Arg634 in the αC helix and Arg934 in the C-lobe, rigidifying the activation loop (residues 953–990, partially disordered) and ordering helix αG to create the eIF2α substrate-binding surface, while luminal domain oligomerization by misfolded proteins drives a "line-up" trans-autophosphorylation mechanism between adjacent PERK dimers. Activated pThr980-PERK phosphorylates eIF2α at Ser51, globally attenuating cap-dependent translation while selectively upregulating ATF4 translation via uORF1 bypass, triggering integrated stress response (ISR) genes for antioxidant defense such as NRF2, protein folding chaperones, amino acid metabolism, and autophagy to restore ER proteostasis under accumulation of unfolded proteins from nutrient deprivation, redox imbalance, or calcium dysregulation. This adaptive pathway protects secretory cells like pancreatic β-cells from ER overload during development and glucose stimulation; pathologically, chronic hyperactivation exhausts adaptation, leading to apoptosis via CHOP/ATF4 induction in diabetes (β-cell failure), neurodegeneration such as Alzheimer's and prion diseases, and ischemia-reperfusion injury, while PERK loss impairs the UPR, causing proinsulin misfolding. Therapeutic PERK inhibitors show promise in prion disease and cancer by blocking ISR-driven survival.

References
https://pubmed.ncbi.nlm.nih.gov/21543844/ https://pubmed.ncbi.nlm.nih.gov/25925385/

Reference Table for Selecting PVDF Membrane Pore Size Specifications

Protein Size (kDa)	PVDF Transfer Membrane Pore Size (μm)
< 10	0.22
10-20	0.22
20-30	0.45
30-45	0.45
45-70	0.45
80-100	0.45
100-140	0.45
> 140	0.45

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Protein Size (kDa)	Separating Gel Percentage
4-40	20%
12-45	15%
10-70	12.5%
15-100	10%
25-100	8%
60-210	5%