Phosphorylation of initiation factors

Farrell, P. J., Balkow, K., Hunt, T., Jackson, R. J., andTrachsel, H. (1977). Phosphorylation of initiation factor eIF-2 and the control of reticulocyte protein synthesis. Cell 11, 187-200. 

Phosphorylation of initiation factors appears to be a general method for translational control in eukaryotes. 

Pain, V. M., and Clemens, M. J., 1983, Assembly and breakdown of mammalian protein synthesis initiation complexes Regulation by guanine nucleotides and by phosphorylation of initiation factor eIF-2, Biochemistry 22 726. 

Kim, Y.M., Son, K., Hong, S.J., Green, A., Chen, J.J., Tzeng, E., Hierholzer, C., and Bdliar, T.R. (1998). Inhibition of protein synthesis by nitric oxide correlates with cytostatic activity nitric oxide induces phosphorylation of initiation factor eIF-2 alpha. Mol. Med. 4(3), 179-190. 

Rowlands, A. G., Panniers, R., and Henshaw, E. C. (1988). The catalytic mechanism of guanine nucleotide exchange factor action and competitive inhibition by phosphorylated eukaryotic initiation factor 2.J. Biol. Chem. 263, 5526-5533. 

Wang, X., Li, W., Parra, J.-L., Beugnet, A., and Proud, C. G. (2003). The C-terminus of initiation factor 4E-binding protein 1 contains multiple regulatory features that influence its function and phosphorylation. Mol. Cell. Biol. 23, 1546—1557. 

High concentrations of hemin inhibit the transport of ALA synthase into the mitochondria, where one of the substrates, succinyl-CoA, is formed. Thus, heme synthesis is inhibited until enough globin is made to react with any heme already formed. Low concentrations, or the absence, of hemin is the signal that globin is not needed this protein (and, therefore, globin) synthesis is inhibited. In the absence of hemin, a protein kinase is activated this phosphorylates an initiation factor of (eukaryotic) protein synthesis, eIF-2, which then inhibits polypeptide chain initiation (Chap. 17) and hence inhibits globin synthesis. 

Sharp JW, Ross-Inta CM, Hao S, Rudell JB, Gietzen DW. 2006. Co-localization of phosphorylated extracellular signal-related protein kinases 1/2 (ERK 1/2) and phosphorylated eukaryotic initiation factor 2a (eIF2a) in response to a threonine-devoid diet. J Comp Neurol 494 485-494. (Gives A-P dimension and location of APC cells that may be the primary sensory cells for lAA deficiency)... 

Figure 14.31 EGF signaling pathway. The key steps in the pathway initiated by EGF binding to the EGF receptor. A kinase cascade leads to the phosphorylation of transcription factors and concomitant changes in gene expression.

Type I (IFN-a/P) and type II (IFN-y) IFNs are major lines of defense against viral infection. IFNs mediate direct antiviral effector mechanisms that inhibit multiple steps of viral replication (Samuel 1991 Vilcek and Sen 1996). For example, 2, 5 -oligoadenylate synthetase (2, 5 -OAS) activates ribonuclease L, which degrades mRNA and limits the accumulation of viral transcripts. Protein kinase R blocks translation of viral transcripts by phosphorylating translation initiation factor eIF-2. Mx proteins block influenza, vesicular stomatitis virus, and herpes simplex virus replication by an unknown mechanism. 

LEVIN, D. and LONDON, I.M. Regulation of protein synthesis Activation by double-stranded RNA of a protein kinase that phosphorylates eukaryotic initiation factor 2. Proc. Natl. 

Crude lysates (S10) or ribosomal extracts from L cell cultures treated for 24 h by 200 U/ml mouse interferon, when incubated with (32p) y (pp low concentrations of dsRNA (O.O4 - 0.4 M-g/nil poly rI rC), demonstrate an increased phosphorylation of several endogenous proteins (4"9) Among these, proteins 67 and 55 (67,000 and 55,000 MW in SDS) are most prominent. Protein 55 comigrates by polyacrylamide gel electrophoresis with the small subunit of initiation factor eIF-2 (Figure 2). Interferon-treated cell extracts contain a dsRNA-dependent protein kinase phosphorylating this subunit of eIF-2, this activity being more... 

There are four main canonical response pathways to manage unfolded proteins via unfolded protein response (UPR) signaling and HSP. PKR-related ER kinase (PERK) is one of receptors to detect ER stress at the ER lumen, which normally binds with BIP (GRP78) (Samali and 2010). When unfolded protein binds to BIP and dissociates from BIP/PERK complex, PERK becomes active and phosphorylates eukaryotic initiation factor 2 initiation factor 2a (eIF2) (Samali etal. 2010). Phosphory-... 

Small RNAs may also be involved in regulating the translation of mRNA in eukaryotic cells. Of the stimulatory RNAs, the best characterized is a small RNA of about 160 nucleotides, which accumulates in cells after infection with adenovirus. This virus-associated RNA, VA-RNAi, which is required to maintain general protein synthesis, acts by inhibiting the phosphorylation of the alpha subunit of initiation factor eIF-2. 

Siekierka, J., Mauser, L., and Ochoa, S., 1982, Mechanism of polypeptide chain initiation in eukaryotes and its control by phosphorylation of the a subunit of initiation factor 2, Proc. Natl. Acad. Sci. USA 79 2537. 

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