Phosphorylation of the a subunit of eukaryotic initiation factor 2 is a well documented mechanism of down regulating protein synthesis under a variety of stress conditions. Eukaryotic initiation factor 2 binds GTP and Met-tRNAi and transfers the Met-tRNA to the 40S subunit to form the 43S preinitiation complex (1,2). For eIF2 to promote a new round of translation initiation, GDP must be exchanged for GTP, a reaction catalyzed by eIF2B (1,2). Kinases activated by viral infection (PKR), endoplasmic reticulum stress (PERK/PEK), amino acid deprivation (GCN2) and hemin deficiency (HRI) can phosphorylate the a subunit of eIF2 (3,4). This phosphorylation stabilizes the eIF2-GDP-eIF2B complex, inhibiting the turnover of eIF2B. Induction of PKR by IFN-g and TNF-a, or stress provoked by depletion of endoplasmic reticulum calcium levels, induces potent phosphorylation of eIF2a at Ser51 (5,6). eIF2B, a guanine nucleotide exchange factor, is composed of 5 subunits, the largest of which is eIF2B-e (7). Multiple in vivo phosphorylation sites have been identified on eIF2B-e (8). Casein Kinase II can phosphorylate eIF2B-e 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-e phosphorylation site, Ser466, can be phosphorylated by casein kinase I.
Product | Size | List | Your Price | Qty | Ext Price | ||||
---|---|---|---|---|---|---|---|---|---|
Subtotal: | Subtotal: | ||||||||
Subtotal: | Subtotal: | ||||||||
Total Coupon Savings: | Total Coupon Savings: | () | |||||||
Your cart is currently empty. | |||||||||
- Coupon Code |