Cell Signaling Technology

Product Pathways - Translational Control

eIF2B-ε Antibody #3595

Applications Reactivity Sensitivity MW (kDa) Source
W H M R Mk Endogenous 85 Rabbit

Applications Key:  W=Western Blotting
Reactivity Key:  H=Human  M=Mouse  R=Rat  Mk=Monkey
Species cross-reactivity is determined by Western blot.

Specificity / Sensitivity

eIF2B-epsilon Antibody detects endogenous levels of total eIF2B-epsilon protein.

Source / Purification

Polyclonal antibodies are produced by immunizing rabbits with a synthetic peptide (KLH-coupled) corresponding to amino acids near the middle of human eIF2B-epsilon. Antibodies are purified by protein A and peptide affinity chromatography.

Western Blotting

Western Blotting

Western blot analysis of extracts from HT29 cells using eIF2B-epsilon Antibody.

Background

Phosphorylation of the eukaryotic initiation factor 2 (eIF2) α subunit is a well-documented mechanism to downregulate protein synthesis under a variety of stress conditions. Eukaryotic initiation factor 2 binds GTP and Met-tRNAi and transfers Met-tRNA to the 40S subunit to form the 43S preinitiation complex (1,2). eIF2 promotes a new round of translation initiation by exchanging GDP for GTP, a reaction catalyzed by eIF2B (1,2). Kinases that are activated by viral infection (PKR), endoplasmic reticulum stress (PERK/PEK), amino acid deprivation (GCN2) or heme deficiency (HRI) can phosphorylate the α subunit of eIF2 (3,4). This phosphorylation stabilizes the eIF2-GDP-eIF2B complex and inhibits the turnover of eIF2B. Induction of PKR by IFN-γ and TNF-α induces potent phosphorylation of eIF2α at Ser51 (5,6).

eIF2B, a guanine nucleotide exchange factor, is composed of 5 subunits, the largest of which is eIF2B-epsilon (7). Multiple in vivo phosphorylation sites have been identified on eIF2B-epsilon (8). Casein Kinase II can phosphorylate eIF2B-epsilon at Ser717/718 to allow for association with its substrate eIF2. Phosphorylation at Ser544 allows GSK-3 to phosphorylate the key regulatory site Ser540. A fifth eIF2B-epsilon phosphorylation site, Ser466, can be phosphorylated by casein kinase I.

  1. Kimball, S.R. (1999) Int. J. Biochem. Cell Biol. 31, 25-29.
  2. De Haro, C. et al. (1996) FASEB J. 10, 1378-1387.
  3. Kaufman, R.J. (1999) Genes Dev. 13, 1211-1233.
  4. Sheikh, M.S. and Fornace Jr., A.J. (1999) Oncogene 18, 6121-6128.
  5. Cheshire, J.L. et al. (1999) J. Biol. Chem. 274, 4801-4806.
  6. Zamanian-Daryoush, M. et al. (2000) Mol. Cell. Biol. 20, 1278-1290.
  7. Fabian , J. R. et al. (1997) J. Biol. Chem. 272, 12359-12365.
  8. Wang, X. et al. (2001) EMBO J. 20, 4349-4359.

Application References

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Companion Products

This product is for in vitro research use only and is not intended for use in humans or animals. This product is not intended for use as therapeutic or in diagnostic procedures.

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